Affinage · Plasmodium

CDPK1

PF3D7_0217500 · calcium-dependent protein kinase 1

Annotated
2026-09-07
63 papers in source corpus 32 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_0217500 (CDPK1) is a calcium-directly-activated serine/threonine protein kinase that coordinates the motility, secretory, and egress machinery driving Plasmodium erythrocyte invasion and sexual-stage development (PMID:8440720, PMID:28680058). Its enzymatic activity is switched on intramolecularly: the C-terminal EF-hand/calmodulin-like domain binds Ca2+ (EF-hand sites I and II being decisive) and engages the junction domain P3 region to relieve autoinhibition and activate the kinase without calmodulin, a regulatory interface whose disruption blocks microneme discharge and invasion (PMID:8440720, PMID:8142371, PMID:23204525). The protein is dually acylated through an N-terminal myristoylation-plus-palmitoylation-plus-basic-cluster module that targets it to the parasite membrane periphery; palmitoylation is dynamic and, in P. yoelii, is delivered by the IMC palmitoyl-acyl-transferase DHHC2, tying membrane localization to microneme secretion and invasion (PMID:15491359, PMID:32003970, PMID:35775739). At its membrane location CDPK1 phosphorylates components of the glideosome actomyosin motor (MTIP at Ser47 and GAP45 at multiple serines) and the adhesin adaptor MTRAP, and phosphorylates PfSERA5 to enhance its protease activity and promote merozoite egress (PMID:18768477, PMID:19549500, PMID:29716996, PMID:27607074). CDPK1 is embedded in a signalling network: it acts downstream of the cGMP-dependent kinase PfPKG, phosphorylates the PfPKA regulatory subunit, and assembles a phospho-dependent Pf14-3-3I–PfPKA-R complex required for microneme secretion and invasion (PMID:26149123, PMID:28680058, PMID:32817103, PMID:32484216). Genetic ablation confirms CDPK1 is essential for P. falciparum asexual growth, invasion, and gametogenesis, whereas in P. berghei it is dispensable in blood and liver stages and required instead for sexual mosquito-stage development and optimal sporozoite motility (PMID:29311293, PMID:24265753, PMID:32866196, PMID:22817984).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    Establishing that CDPK1 is a bona fide calcium-activated kinase answered whether a single polypeptide could couple Ca2+ sensing to catalysis without an accessory calmodulin.

    Evidence Recombinant full-length protein in E. coli with Ca2+-dependent in vitro kinase assay

    PMID:8440720

    Open questions at the time
    • No physiological substrates identified at this stage
    • Mechanism of intramolecular activation not resolved
  2. 1994 High

    Dissecting the four EF-hand motifs defined which Ca2+-binding sites drive the activating conformational change, localizing the regulatory switch to sites I and II.

    Evidence Site-directed mutagenesis of EF-hand motifs with in vitro kinase assay, CD, and 45Ca2+ binding; plus biochemical characterization of substrate preference, autophosphorylation, and membrane-fraction localization

    PMID:7808482 PMID:8142371

    Open questions at the time
    • Structural basis of EF-hand-to-kinase coupling not defined
    • In vitro substrates (casein, histone) not physiological targets
  3. 2004 High

    Identifying the N-terminal acylation/basic-cluster module answered how a soluble kinase is anchored to membranes and directed to secretory compartments.

    Evidence N-terminal mutagenesis, GFP reporter targeting, in vitro myristoylation, and immunogold EM in P. falciparum

    PMID:15491359

    Open questions at the time
    • Enzyme responsible for palmitoylation not identified here
    • Functional consequence of membrane targeting not tested genetically
  4. 2008 High

    Linking CDPK1 to the glideosome motor and demonstrating essentiality established its role in the invasion/egress machinery and validated it as a drug target.

    Evidence Failed gene disruption plus inhibitor phenotyping; in vitro phosphorylation of MTIP (Ser47) and GAP45 with MS site mapping, IFA localization, and invasion-blocking inhibitors

    PMID:18454143 PMID:18768477

    Open questions at the time
    • Functional impact of motor-component phosphorylation not directly shown
    • Essentiality inferred from failed disruption rather than conditional knockout
  5. 2009 High

    Comprehensive mapping of GAP45 phosphosites clarified the extent and regulatory logic of CDPK1 modification of a motor anchor.

    Evidence In vitro phosphorylation with nano-UPLC-MS/MS, IMAC enrichment, and synthetic phosphopeptide controls

    PMID:19549500

    Open questions at the time
    • Physiological occupancy of these sites in parasites not established
    • Functional readout of individual sites absent
  6. 2012 High

    Defining the CamLD–junction domain P3 interaction resolved the structural mechanism of intramolecular autoinhibition and provided a peptide tool that blocks invasion.

    Evidence Junction-domain mutagenesis, CamLD–JD binding assay, P3 peptide inhibition, microneme and invasion assays; plus autophosphorylation/NTE mapping and GFP-localization/J-domain knockdown

    PMID:22539638 PMID:23204525 PMID:23548171

    Open questions at the time
    • Full activated-state structure not solved
    • NTE ATP-binding site partly modeling-dependent
  7. 2012 High

    Genetic work in P. berghei revealed a stage-restricted essentiality and an unexpected role for CDPK1 as a translational activator in the developing zygote.

    Evidence Conditional knockdown in P. berghei sexual stages with ribosome footprinting, transcriptional profiling, and mosquito infection assays

    PMID:22817984

    Open questions at the time
    • Molecular mechanism by which CDPK1 activates translation unknown
    • Direct RNA/ribosome targets of CDPK1 not defined
  8. 2013 High

    A clean P. berghei conditional knockout established species-divergent essentiality: dispensable in blood and liver stages, essential only in mosquito sexual stages.

    Evidence Homologous-recombination disruption and conditional knockout with stage-specific phenotyping in P. berghei

    PMID:24265753

    Open questions at the time
    • Basis for divergence from P. falciparum essentiality not explained
    • Redundant kinases masking blood-stage phenotype not identified
  9. 2014 High

    Heterologous rescue of a T. gondii CDPK mutant demonstrated that CDPK1 function requires both membrane localization and kinase activity, and built a surrogate for inhibitor validation.

    Evidence Complementation of T. gondii TgCDPK3 mutant with membrane/kinase-dead mutagenesis and egress assays

    PMID:24550330

    Open questions at the time
    • Native P. falciparum substrates driving egress in this assay not defined
    • Cross-species functional equivalence limits mechanistic inference
  10. 2015 Medium

    Placing CDPK1 downstream of PfPKG and mapping PfAlba1 repression of CDPK1 mRNA situated the kinase within phospho- and translational-control cascades governing egress/invasion.

    Evidence Quantitative phosphoproteomics with PKG chemical/genetic perturbation; RIP-seq of PfAlba1-bound CDPK1 mRNA with translation-state analysis

    PMID:26149123 PMID:26415947

    Open questions at the time
    • PfPKG phosphosite(s) on CDPK1 and their functional consequence not defined
    • Direct effect of PfAlba1 release on CDPK1 protein levels only correlative
  11. 2016 Medium

    Gatekeeper mutation studies exposed pathway compensation, showing PKG-linked activity buffers reduced CDPK1 function.

    Evidence CRISPR/Cas9 T145M substitution with bumped-kinase and PKG inhibitor epistasis and RNA-seq of CDPK5/CDPK6

    PMID:27923926

    Open questions at the time
    • Compensating kinase not directly demonstrated
    • Transcript upregulation not shown to restore function
  12. 2017 High

    Conditional knockdown plus comparative phosphoproteomics confirmed the invasion requirement and revealed CDPK1–PKA crosstalk via phosphorylation of the PKA regulatory subunit.

    Evidence Inducible knockdown, comparative phosphoproteomics, in vitro kinase assay, and invasion assay in P. falciparum

    PMID:28680058

    Open questions at the time
    • Functional output of PfPKA-R phosphorylation on invasion not fully dissected
    • Which substrates are direct versus indirect remains partly open
  13. 2018 High

    Definitive P. falciparum disruption (only tolerated on a low-activity background) and complementation quantified requirements across asexual growth and gametogenesis; PfSERA5 was defined as an egress-promoting substrate.

    Evidence CRISPR/Cas9 disruption with complementation and RNA-seq; co-IP/co-sedimentation/co-immunolocalization of PfSERA5 with in vitro phosphorylation and egress assays

    PMID:29311293 PMID:29716996

    Open questions at the time
    • Mechanism coupling CDPK1 loss to elevated gametocyte transcripts unclear
    • PfSERA5 phosphosite(s) not mapped
  14. 2020 Medium

    Multiple 2020 studies integrated CDPK1 into a membrane-anchored signalling hub—dynamic palmitoylation, MTRAP phosphorylation, a 14-3-3I/PKA-R complex, and RhopH3-linked rhoptry discharge—while P. berghei work defined a sporozoite-motility role.

    Evidence ABE/CuAAC palmitoylation imaging with PAT inhibitor and invasion assays; in vitro MTRAP-CTD phosphorylation/aldolase binding; phosphoproteomics, reciprocal co-IP, gel filtration, SPR and phosphopeptide competition for the Pf14-3-3I–PKA-R complex; RhopH3-S804 phosphomutant with CDPK1 knockdown; P. berghei cKO with cGMP epistasis

    PMID:27607074 PMID:32003970 PMID:32484216 PMID:32817103 PMID:32866196 PMID:33024030

    Open questions at the time
    • Physiological MTRAP phosphorylation by CDPK1 not detected in tagged parasites
    • Direct phosphorylation of RhopH3-S804 by CDPK1 not shown in vitro
    • PAT inhibitor used is not CDPK1-specific
  15. 2022 Medium

    Identifying DHHC2 as the IMC palmitoyl-acyl-transferase acting on CDPK1 connected the acylation-dependent localization to a specific enzyme and to schizont segmentation.

    Evidence TurboID IMC proteomics, palmitome cross-referencing, and conditional DHHC2 depletion with CDPK1 localization in P. yoelii

    PMID:35775739

    Open questions at the time
    • Direct in vitro palmitoylation of CDPK1 by DHHC2 not demonstrated
    • Species-specific relevance to P. falciparum not tested
  16. 2025 Medium

    Characterizing the PfRKIP–CDPK1 relationship in parasites established a substrate-dependent regulatory loop in which hyperphosphorylation releases PfRKIP to permit trans-phosphorylation of other substrates.

    Evidence ELISA binding, IFA co-localization, TurboID proximity biotinylation, in vitro kinase assay, and PEBP-domain docking/mutagenesis in P. falciparum (building on earlier in vitro identification of PfRKIP as substrate/regulator)

    PMID:17123645 PMID:39842334

    Open questions at the time
    • In vivo consequence of PfRKIP regulation on invasion/egress not established
    • Single-lab regulatory model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CDPK1 phosphorylation events are spatiotemporally integrated with dephosphorylation and ubiquitination during the invasion/egress cycle remains unresolved.
  • Functional consequence of the CDPK1–PP7 interaction untested
  • Direct mechanistic link between FBXO1-dependent ubiquitination and CDPK1 phosphorylation not resolved
  • Ordering of substrate phosphorylation events during a single invasion cycle unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
DHHC2 PALMITOYL-ACYL-TRANSFERASE [#26]PF14-3-3I (BINDS PHOSPHO-CDPK1) [#23]PFALBA1 (RNA-BINDING REPRESSOR OF CDPK1 MRNA) [#16]PFPKA-R (SUBSTRATE/COMPLEX MEMBER) [#18, #23]PFPKG (UPSTREAM KINASE) [#15]PFRKIP/PFPE-PB1 (SUBSTRATE AND REGULATOR) [#4, #29]PFSERA5 (INTERACTOR AND SUBSTRATE) [#19]PP7 PROTEIN PHOSPHATASE (CO-IP) [#28]
Complex memberships
Pf14-3-3I–PfPKA-R–CDPK1 phospho-dependent multiprotein complex [#23]

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 CDPK1 (PfCPK) was shown to be a calcium-dependent serine/threonine protein kinase: recombinant full-length protein expressed in E. coli exhibited Ca2+-dependent kinase activity, demonstrating that the C-terminal EF-hand domain directly activates the N-terminal kinase domain without requiring calmodulin. Recombinant expression in E. coli, in vitro kinase assay with Ca2+ dependency The Journal of biological chemistry High 8440720
1994 CDPK1 has four EF-hand calcium-binding sites; EF-hand sites I and II are crucial for both Ca2+-induced conformational change and enzymatic activation (mutation at site II nearly abolishes activity; site I mutations dramatically reduce Ca2+ sensitivity), while sites III and IV have minor effects. Site-directed mutagenesis of individual EF-hand motifs (Glu→Lys or Gln), in vitro kinase assay, circular dichroism, 45Ca2+ binding Biochemistry High 8142371
1994 Purified recombinant CDPK1 preferentially phosphorylates erythrocytic membrane proteins in vitro (with casein and histone H1 as exogenous substrates); the kinase undergoes autophosphorylation on serine and threonine residues; Ca2+ activation is partially replaceable by Mn2+ but not by Zn2+ or Mg2+; calmodulin antagonists inhibit activity; the protein is mainly expressed in ring and schizont stages and localizes to the parasitic membrane-organelle fraction. Protein purification, in vitro kinase assay, 45Ca2+ binding, autophosphorylation assay, subcellular fractionation, immunoblotting Molecular and biochemical parasitology High 7808482
2004 CDPK1 contains three N-terminal membrane-anchor motifs (a myristoylation consensus, a palmitoylation site, and a basic cluster); the protein is myristoylated both endogenously and in vitro; dual acylation plus the basic cluster are required for targeting to the parasitophorous vacuole, as shown by GFP reporter mutagenesis. Immunogold EM localized the endogenous protein to the parasitophorous vacuole and the tubovesicular system. N-terminal mutagenesis, GFP reporter targeting assays, in vitro translation/myristoylation assay, immunogold electron microscopy Molecular microbiology High 15491359
2006 The Plasmodium falciparum RKIP ortholog (PfPE-PB1) is phosphorylated by CDPK1 in vitro (at ~7-fold lower specific activity than casein) and its presence enhances CDPK1 autophosphorylation ~5.5-fold while reducing CDPK1 trans-phosphorylation of casein, indicating PfRKIP acts as both a substrate and a regulator of CDPK1 activity. Recombinant protein purification, in vitro kinase assay (autophosphorylation and substrate phosphorylation) Molecular and biochemical parasitology Medium 17123645
2008 CDPK1 is expressed during late schizogony and in sporozoites; a targeted gene-disruption approach indicated CDPK1 is essential for parasite viability; treatment with 2,6,9-trisubstituted purine inhibitors of CDPK1 causes developmental arrest at late schizont stage, linking CDPK1 to regulation of parasite motility, egress, and invasion. Gene-disruption attempt, in vitro biochemical screen (20,000 compounds), compound treatment phenotyping Nature chemical biology Medium 18454143
2008 CDPK1 phosphorylates two glideosome motor complex components—MTIP (primarily at serine 47) and GAP45 (at two sites, one confirmed in parasite lysates phosphopeptides)—in vitro; CDPK1 localizes to the periphery of merozoites by indirect immunofluorescence; the kinase inhibitor K252a inhibits both CDPK1 activity and host cell invasion. In vitro kinase assay with recombinant substrates, mass spectrometry phosphopeptide mapping, indirect immunofluorescence, inhibitor treatment The Journal of biological chemistry High 18768477
2009 CDPK1 phosphorylates GAP45 in vitro at nine sites (Ser31, Ser89, Ser103, Ser109, Ser121, Ser149, Ser156, Thr158, Ser173); phosphorylation at Ser156/Thr158 is mutually exclusive and alters susceptibility of adjacent sites to proteolytic cleavage. In vitro phosphorylation by recombinant CDPK1, nano-UPLC-MS/MS, Ga(III)-IMAC phosphopeptide enrichment, synthetic phosphopeptide controls Analytical biochemistry High 19549500
2012 The C-terminal calmodulin-like domain (CamLD) of CDPK1 binds the P3 region (Leu356–Thr370) of the junction domain (JD) in a calcium-dependent manner; mutagenesis of conserved hydrophobic residues in the JD (F363A/I364A, L356A, F350A) abolishes kinase activity; a P3 peptide inhibits CDPK1 activity, blocks microneme discharge, and blocks erythrocyte invasion, directly linking the CamLD–JD interaction to CDPK1 regulation and invasion. Site-directed mutagenesis of JD, in vitro binding assay (CamLD–JD), peptide inhibition, microneme secretion assay, erythrocyte invasion assay The Journal of biological chemistry High 23204525
2012 In P. berghei, CDPK1 is essential in sexual mosquito-stage parasites: knockdown caused developmental arrest and prevented mosquito transmission independently of its proposed role in motility. Translational and transcriptional profiling of arrested parasites revealed that CDPK1 translationally activates mRNA species in the developing zygote that in macrogametes remain repressed via their 3' and 5' UTRs. Conditional knockdown in P. berghei sexual stages, translational profiling (ribosome footprinting), transcriptional profiling, mosquito infection assays Cell host & microbe High 22817984
2012 CDPK1 tagged with GFP localizes to the parasite plasma membrane of replicating and invasive forms and young intracellular parasites; conditional inhibition via the CDPK1 auto-inhibitory J-domain fused to GFP (J-GFP-DD) specifically binds CDPK1 in vitro and causes arrest in early schizogony when expressed in vivo, pointing to an early schizont function. GFP tagging of endogenous CDPK1, live imaging, destabilization-domain knockdown, in vitro binding of J-GFP fusion to CDPK1, inducible J-GFP-DD expression in parasites The Biochemical journal High 23548171
2012 CDPK1 phosphorylates GAP45 in vitro at S89, S103, and S149; this is regulated by PLC and calcium signaling; CDPK1 and PfPKB are both responsible for these GAP45 phosphorylation events; however, replacing these serine residues with alanine or aspartate had no apparent effect on GAP45 assembly into the motor complex or its subcellular localization. In vitro kinase assay, site-directed mutagenesis of GAP45 phosphosites, GFP tagging for localization, phosphorylation timing analysis in parasite development PloS one Medium 22479457 22558243
2012 Mass spectrometry revealed CDPK1 autophosphorylation at multiple sites; mutations in the regulatory/CAD domain affect both active and inactive kinase conformations; the N-terminal extension (NTE) of CDPK1 is important for activation and contains an ATP-binding site. Mass spectrometry (autophosphorylation site mapping), site-directed mutagenesis, molecular modeling FASEB journal Medium 22539638
2013 P. berghei CDPK1 is dispensable for erythrocytic invasion, intra-erythrocytic development, sporozoite invasion of hepatocytes, hepatocyte egress, and subsequent erythrocytic cycle (conditional knockout); CDPK1 in P. berghei is essential only in mosquito sexual stages. Homologous recombination gene disruption, conditional knockout (cKO), phenotypic characterization across life stages PloS one High 24265753
2014 Expression of PfCDPK1 in Toxoplasma gondii TgCDPK3 mutant rescues calcium ionophore-induced egress defect; rescue requires both plasma membrane localization and kinase activity of CDPK1; this established a surrogate system where CDPK1-specific inhibitors could be functionally validated. Heterologous complementation in T. gondii, mutagenesis of kinase activity and membrane-targeting motifs, egress assay, pharmacological inhibition Antimicrobial agents and chemotherapy High 24550330
2015 CDPK1 is phosphorylated by PfPKG (cGMP-dependent protein kinase), as shown by quantitative global phosphoproteomics using PKG chemical inhibition and genetic tools, positioning CDPK1 downstream of PfPKG in a signaling cascade regulating egress and invasion. Quantitative phosphoproteomics with PKG chemical inhibitor and conditional genetic tools Nature communications High 26149123
2015 CDPK1 mRNA is bound by PfAlba1 RNA-binding protein in trophozoites, repressing translation; release of CDPK1 mRNA from the PfAlba1 complex in mature stages correlates with protein synthesis, indicating PfAlba1-mediated translational repression of CDPK1 in trophozoites. RIP-seq (deep sequencing of affinity-purified PfAlba1-associated RNAs), overexpression of epitope-tagged PfAlba1, mRNA homeostasis and translation analysis Genome biology Medium 26415947
2016 Reduced transphosphorylation activity of CDPK1 caused by the T145M gatekeeper mutation is compensated in the parasite through PKG activity (or a kinase under PKG regulation), with CDPK5 and CDPK6 transcripts significantly upregulated in T145M parasites. CRISPR/Cas9 gatekeeper substitution, bumped kinase inhibitor (BKI 1294) dose-response in vitro and in parasites, PKG inhibitor (C2) sensitivity testing, RNA-seq transcript quantification mBio Medium 27923926
2017 Conditional knockdown of CDPK1 established it is critical for host erythrocyte invasion; comparative phosphoproteomics identified CDPK1 substrates including Inner Membrane Complex proteins and glideosome-actomyosin motor components; CDPK1 phosphorylates the PfPKA regulatory subunit (PfPKA-R) and thereby regulates PfPKA activity in the parasite. Conditional knockdown (inducible), comparative phosphoproteomics, in vitro kinase assay, erythrocyte invasion assay Nature communications High 28680058
2018 PfCDPK1 interacts with PfSERA5 (immunoprecipitation, co-sedimentation, co-immunolocalization) and phosphorylates PfSERA5 in vitro in a Ca2+-dependent manner, enhancing its proteolytic activity; the CDPK1 inhibitor purfalcamine blocked PfSERA5 phosphorylation and activation both in vitro and in schizonts, blocking merozoite egress. Immunoprecipitation (anti-PfSERA5 followed by MS), co-sedimentation, co-immunolocalization, in vitro kinase assay, purfalcamine inhibitor treatment, egress assay The Journal of biological chemistry High 29716996
2018 CDPK1 was successfully disrupted in P. falciparum only in a background with the T145M gatekeeper mutation (reduced activity); KO parasites show slow asexual growth, defects in both male and female gametogenesis, and cannot establish mosquito infection; complementation with full-length CDPK1 partially rescues asexual growth and mosquito infection; CDPK1 KO schizonts show elevated gametocyte-specific gene transcripts. CRISPR/Cas9 gene disruption, complementation, phenotypic analysis (growth rate, gametogenesis, mosquito infection), RNA-seq PNAS High 29311293
2020 CDPK1 is dynamically palmitoylated in P. falciparum merozoites and localizes to the merozoite membrane; exposure to low [K+] activates palmitoyl acyl transferase (PAT) activity, which is required for microneme secretion; the PAT inhibitor 2-bromopalmitate blocks microneme secretion and RBC invasion, linking dynamic palmitoylation of CDPK1 to its membrane localization and invasion function. Acyl biotin exchange (ABE) chemistry, copper-catalyzed alkyne-azide chemistry (CuAAC) imaging, confocal microscopy, pharmacological inhibition, microneme secretion assay, RBC invasion assay ACS infectious diseases Medium 32003970
2020 CDPK1 phosphorylates MTRAP cytoplasmic tail domain in vitro, and this phosphorylation increases MTRAP affinity for aldolase ~10-fold, suggesting CDPK1-mediated phosphorylation dynamically modulates coupling of the actomyosin motor to surface adhesins during invasion. In vitro kinase assay (CDPK1 + MTRAP CTD), direct binding assay (MTRAP CTD vs. aldolase), single amino acid substitutions in MTRAP CTD PloS one Medium 27607074
2020 CDPK1 is phosphorylated in a Ca2+-dependent manner in merozoites; Pf14-3-3I binds phosphorylated CDPK1 (at the canonical Mode I RXXpS motif centered on 61KLGpS64) and assembles a multiprotein signaling complex together with PfPKA-R; disruption of this complex with a competing phosphopeptide inhibits microneme secretion and RBC invasion. Quantitative phosphoproteomics (high/low K+ conditions), co-immunoprecipitation, gel filtration chromatography, ELISA, SPR, molecular dynamics simulation, phosphopeptide competition assay, invasion assay mBio High 32484216 32817103
2020 CDPK1 in P. berghei is required for optimal sporozoite motility and hepatocyte invasion; increased cGMP can compensate for loss of CDPK1 (and CDPK5) during sporozoite invasion but not for loss of CDPK4; CDPK1 expression is downregulated after sporozoite invasion. Conditional knockout (cKO) in P. berghei, sporozoite motility assay, hepatocyte invasion assay, cGMP supplementation rescue experiment PLoS pathogens Medium 32866196
2020 CDPK1 is a candidate kinase for RhopH3 serine 804 phosphorylation; CDPK1 knockdown reduces RhopH3 secretion from the parasite, linking CDPK1 activity to rhoptry discharge during invasion. CRISPR-Cas9 phosphomutant (S804A) of RhopH3, conditional knockdown of CDPK1, rhoptry secretion assay mBio Medium 33024030
2022 DHHC2 palmitoyl-acyl-transferase, the major resident PAT of the P. yoelii inner membrane complex (IMC), palmitoylates CDPK1 and GAP45, and this palmitoylation is required for their IMC localization; depletion of DHHC2 leads to defective schizont segmentation. TurboID proximity labeling proteomics, IMC-proteome compilation, palmitome cross-referencing, conditional DHHC2 depletion, fluorescence localization of CDPK1 and GAP45 in DHHC2-depleted parasites eLife Medium 35775739
2023 FBXO1-dependent ubiquitination interplays with CDPK1-mediated phosphorylation in P. berghei; ubiquitinomic surveys show FBXO1-dependent ubiquitination of proteins important for egress and IMC organization, with an additional layer of regulation via CDPK1 phosphorylation. Ubiquitinomics (proteomics of FBXO1-dependent ubiquitinated proteins), co-immunoprecipitation, genetic disruption of FBXO1 Nature communications Low 36898988
2024 PP7 (protein phosphatase 7) interacts with CDPK1 in P. falciparum, as determined by co-immunoprecipitation, consistent with a role for CDPK1 in the calcium signaling network that PP7 participates in. Co-immunoprecipitation, conditional disruption of PP7, phosphoproteomics mBio Low 39387582
2025 PfRKIP interacts with CDPK1 within P. falciparum parasites (confirmed by immunofluorescence and proximity biotinylation); PfRKIP regulates CDPK1 kinase activity; in the presence of a substrate, CDPK1 hyper-phosphorylates PfRKIP causing its dissociation from CDPK1, thereby allowing CDPK1 to trans-phosphorylate other substrates. ELISA (in vitro binding), immunofluorescence assay (co-localization in parasites), proximity biotinylation (TurboID), in vitro kinase assay, in silico docking and mutagenesis of PEBP domain Biochemical and biophysical research communications Medium 39842334

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility. Nature chemical biology 180 18454143
2008 The motor complex of Plasmodium falciparum: phosphorylation by a calcium-dependent protein kinase. The Journal of biological chemistry 147 18768477
2012 A Plasmodium calcium-dependent protein kinase controls zygote development and transmission by translationally activating repressed mRNAs. Cell host & microbe 143 22817984
2015 Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. Nature communications 136 26149123
2012 The Plasmodium falciparum schizont phosphoproteome reveals extensive phosphatidylinositol and cAMP-protein kinase A signaling. Journal of proteome research 112 23025827
2015 A genome-scale vector resource enables high-throughput reverse genetic screening in a malaria parasite. Cell host & microbe 104 25732065
2004 Export of Plasmodium falciparum calcium-dependent protein kinase 1 to the parasitophorous vacuole is dependent on three N-terminal membrane anchor motifs. Molecular microbiology 92 15491359
2017 PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum. Nature communications 80 28680058
1993 Gene structure and expression of an unusual protein kinase from Plasmodium falciparum homologous at its carboxyl terminus with the EF hand calcium-binding proteins. The Journal of biological chemistry 80 8440720
2012 Characterization of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) and its role in microneme secretion during erythrocyte invasion. The Journal of biological chemistry 79 23204525
1994 Calcium-binding properties of a calcium-dependent protein kinase from Plasmodium falciparum and the significance of individual calcium-binding sites for kinase activation. Biochemistry 68 8142371
2018 PfCDPK1 is critical for malaria parasite gametogenesis and mosquito infection. Proceedings of the National Academy of Sciences of the United States of America 64 29311293
2009 Identification and characterization of novel small molecules as potent inhibitors of the plasmodial calcium-dependent protein kinase 1. Biochemistry 57 19507895
2012 Subcellular location, phosphorylation and assembly into the motor complex of GAP45 during Plasmodium falciparum schizont development. PloS one 55 22479457
2015 The PfAlba1 RNA-binding protein is an important regulator of translational timing in Plasmodium falciparum blood stages. Genome biology 50 26415947
2014 The gatekeeper residue and beyond: homologous calcium-dependent protein kinases as drug development targets for veterinarian Apicomplexa parasites. Parasitology 49 24927073
2015 Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development. Antimicrobial agents and chemotherapy 47 26711771
2013 Inhibition of Plasmodium falciparum CDPK1 by conditional expression of its J-domain demonstrates a key role in schizont development. The Biochemical journal 45 23548171
2016 Biochemical Screening of Five Protein Kinases from Plasmodium falciparum against 14,000 Cell-Active Compounds. PloS one 44 26934697
1994 Plasmodium falciparum calcium-dependent protein kinase phosphorylates proteins of the host erythrocytic membrane. Molecular and biochemical parasitology 42 7808482
2013 Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). Bioorganic & medicinal chemistry letters 39 23570789
2016 Reduced Activity of Mutant Calcium-Dependent Protein Kinase 1 Is Compensated in Plasmodium falciparum through the Action of Protein Kinase G. mBio 36 27923926
2014 Optimization of an imidazopyridazine series of inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). Journal of medicinal chemistry 36 24689770
2012 Calcium dependent protein kinase 1 and calcium fluxes in the malaria parasite. Microbes and infection 36 22584104
2014 Biochemical and antiparasitic properties of inhibitors of the Plasmodium falciparum calcium-dependent protein kinase PfCDPK1. Antimicrobial agents and chemotherapy 30 25070106
2013 Plasmodium berghei calcium dependent protein kinase 1 is not required for host cell invasion. PloS one 28 24265753
2013 Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole linked analogues. Bioorganic & medicinal chemistry letters 26 24035097
2020 Overlapping and distinct roles of CDPK family members in the pre-erythrocytic stages of the rodent malaria parasite, Plasmodium berghei. PLoS pathogens 22 32866196
2018 Calcium-dependent phosphorylation of Plasmodium falciparum serine repeat antigen 5 triggers merozoite egress. The Journal of biological chemistry 22 29716996
2022 Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite. eLife 20 35775739
2012 Novel insights into the regulation of malarial calcium-dependent protein kinase 1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20 22539638
2012 Regulation of Plasmodium falciparum glideosome associated protein 45 (PfGAP45) phosphorylation. PloS one 20 22558243
2009 Protein phosphorylation influences proteolytic cleavage and kinase substrate properties exemplified by analysis of in vitro phosphorylated Plasmodium falciparum glideosome-associated protein 45 by nano-ultra performance liquid chromatography-tandem mass spectrometry. Analytical biochemistry 20 19549500
2020 Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite. mBio 18 33024030
2020 Development of novel anti-malarial from structurally diverse library of molecules, targeting plant-like CDPK1, a multistage growth regulator of P. falciparum. The Biochemical journal 17 32401306
2019 Integrative Multi-Kinase Approach for the Identification of Potent Antiplasmodial Hits. Frontiers in chemistry 17 31824917
2014 Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs. Antimicrobial agents and chemotherapy 17 24550330
2023 The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei. Nature communications 16 36898988
2006 Raf kinase inhibitor protein affects activity of Plasmodium falciparum calcium-dependent protein kinase 1. Molecular and biochemical parasitology 14 17123645
2020 Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex during Red Blood Cell Invasion by Plasmodium falciparum Merozoites. mBio 12 32817103
2017 Exploring the structural requirements in multiple chemical scaffolds for the selective inhibition of Plasmodium falciparum calcium-dependent protein kinase-1 (PfCDPK-1) by 3D-pharmacophore modelling, and docking studies. SAR and QSAR in environmental research 12 28562086
2020 Molecular dynamics simulations and biochemical characterization of Pf14-3-3 and PfCDPK1 interaction towards its role in growth of human malaria parasite. The Biochemical journal 10 32484216
2020 Protein S-Palmitoylation Is Responsive to External Signals and Plays a Regulatory Role in Microneme Secretion in Plasmodium falciparum Merozoites. ACS infectious diseases 9 32003970
2019 Targeted Inhibition of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 with a Constrained J Domain-Derived Disruptor Peptide. ACS infectious diseases 8 30746930
2016 Computational strategies to explore antimalarial thiazine alkaloid lead compounds based on an Australian marine sponge Plakortis Lita. Journal of biomolecular structure & dynamics 7 27494993
2016 The Binding of Plasmodium falciparum Adhesins and Erythrocyte Invasion Proteins to Aldolase Is Enhanced by Phosphorylation. PloS one 7 27607074
2021 cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition of Plasmodium falciparum Blood Stages. Frontiers in microbiology 6 34108954
2020 Targeting Plasmodium with constrained peptides and peptidomimetics. IUBMB life 5 32037730
2024 Biological evaluation of novel side chain containing CQTrICh-analogs as antimalarials and their development as PfCDPK1 kinase inhibitors. Heliyon 4 38327451
2022 7H-Pyrrolo[2,3-d]pyrimidine-4-amines as Potential Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinases. ChemMedChem 4 36106757
2023 Predicting Plasmodium falciparum kinase inhibitors from antimalarial medicinal herbs using computational modeling approach. In silico pharmacology 3 38130691
2025 Plasmodium falciparum raf kinase inhibitor is a lipid binding protein that interacts with and regulates the activity of PfCDPK1, an essential plant-like kinase required for red blood cell invasion. Biochemical and biophysical research communications 2 39842334
2024 Plasmodium falciparum protein phosphatase PP7 is required for early ring-stage development. mBio 2 39387582
2020 Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development. Tropical biomedicine 2 33612795
2023 Amodiaquine drug pressure selects nonsynonymous mutations in pantothenate kinase 1, diacylglycerol kinase, and phosphatidylinositol-4 kinase in Plasmodium berghei ANKA. Open research Africa 1 38915420
2022 Allosteric regulation of the inactive to active state conformational transition in CDPK1 protein of Plasmodium falciparum. International journal of biological macromolecules 1 35709874
2021 Chemogenomic Fingerprints Associated with Stage-Specific Gametocytocidal Compound Action against Human Malaria Parasites. ACS infectious diseases 1 34569223
2026 Corrigendum to "Plasmodium falciparum Raf kinase inhibitor is a lipid binding protein that interacts with and regulates the activity of PfCDPK1, an essential plant-like kinase required for red blood cell invasion" [Biochem. Biophys. Res. Commun. 749 (2025) 151350]. Biochemical and biophysical research communications 0 41633918
2026 Harnessing the Quinoline Scaffold toward Discovery and Development of Antimalarials. Journal of medicinal chemistry 0 42213905
2026 Proteogenomic Analysis of CDPK1 Mutant in Plasmodium falciparum. Omics : a journal of integrative biology 0 42300840
2025 Gefitinib as an antimalarial: unveiling its therapeutic potential. Inflammopharmacology 0 40019687
2025 Versatile Imidazole Scaffold with Potent Activity against Multiple Apicomplexan Parasites. ACS infectious diseases 0 40339062
2024 Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases. Journal of visualized experiments : JoVE 0 39651747