Affinage

PRKCI

Protein kinase C iota type · UniProt P41743

Round 2 corrected
Length
596 aa
Mass
68.3 kDa
Annotated
2026-04-28
97 papers in source corpus 26 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRKCI encodes protein kinase C iota, an atypical serine/threonine kinase that functions as the catalytic component of the evolutionarily conserved PAR3–PAR6–aPKC polarity complex, where it is essential for establishing apicobasal epithelial polarity, tight junction biogenesis, oriented cell division, and tissue morphogenesis in contexts ranging from cardiac development to neural progenitor self-renewal (PMID:10934474, PMID:11257119, PMID:16319113, PMID:19449304). Through its PB1 domain, PKCι scaffolds with p62/SQSTM1 and RIP to activate NF-κB by directly phosphorylating IKKβ at Ser177/Ser181, and it sustains autophagy flux via the PIK3CA/AKT–mTOR axis in pancreatic acinar cells (PMID:10022904, PMID:10356400, PMID:35159064). In oncogenic settings, PKCι phosphorylates SOX2 to drive Hedgehog ligand production, stabilizes c-Myc (Ser21) and TGFβR1 against proteasomal degradation, and phosphorylates Jak2 (Ser633) to promote STAT3-dependent angiogenesis (PMID:24525231, PMID:41188443, PMID:40382656, PMID:40840329). Rare loss-of-function PRKCI variants cause Van der Woude syndrome by disrupting periderm differentiation upstream of IRF6 (PMID:40902599).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1993 High

    Molecular cloning of PRKCI established it as a novel atypical PKC isoform most closely related to PKCζ, possessing serine/threonine kinase activity but lacking the Ca²⁺-binding and dual cysteine-rich motifs of conventional PKCs, thereby defining a distinct regulatory input logic for this branch of the PKC family.

    Evidence cDNA cloning, Northern/Western blot, in vitro kinase assay in CHO-K1 cells

    PMID:8226978

    Open questions at the time
    • No endogenous substrates identified
    • Tissue-specific expression pattern not fully mapped
    • Activation mechanism in cells unknown
  2. 1996 High

    Identification of Par-4 as a specific inhibitor of atypical PKCs (including PKCι) that promotes apoptosis established that PKCι kinase activity functions as a pro-survival signal, answering whether atypical PKCs have roles beyond conventional PKC-regulated pathways.

    Evidence Co-immunoprecipitation, in vitro kinase assay, kinase-dead mutant rescue in NIH-3T3 cells

    PMID:8797824

    Open questions at the time
    • Mechanism by which Par-4 inhibits aPKC catalytic activity not resolved
    • Downstream survival substrates not identified
  3. 1999 High

    Demonstration that PKCι directly phosphorylates IKKβ (Ser177/Ser181) and that the scaffold protein p62 bridges PKCι to RIP in the TNFα pathway placed PKCι at a defined position in NF-κB activation, resolving how atypical PKCs connect receptor signaling to IKK.

    Evidence In vitro kinase assay, site-directed mutagenesis, dominant-negative transfection, antisense p62, NF-κB reporter

    PMID:10022904 PMID:10356400

    Open questions at the time
    • Relative contribution of PKCι vs. PKCζ to NF-κB in vivo not resolved
    • Structural basis of p62–aPKC interaction unknown at this time
  4. 2000 High

    Discovery that PKCι forms a ternary complex with Par6, Par3, and Cdc42-GTP at tight junctions revealed the conserved polarity machinery through which PKCι controls epithelial apicobasal polarity, answering how a kinase connects Rho-family GTPase signaling to junction formation.

    Evidence Yeast two-hybrid, reciprocal Co-IP, dominant-negative expression, tight junction permeability assay in epithelial cells

    PMID:10934474 PMID:11257119

    Open questions at the time
    • Direct phosphorylation substrates within the polarity complex not identified
    • How kinase activity remodels the complex unclear
  5. 2003 High

    Mapping the PB1 domain as the module mediating PKCι interactions with both p62 and Par6 unified the NF-κB and polarity functions under a single structural interface, explaining how one kinase is routed to distinct pathways through competitive PB1-mediated scaffolding.

    Evidence Mutagenesis of basic/acidic charge residues, Co-IP, yeast two-hybrid

    PMID:12813044

    Open questions at the time
    • Whether p62 and Par6 binding is mutually exclusive in vivo not tested
    • No crystal structure of the PB1 heterodimer at this time
  6. 2005 High

    Genetic studies in zebrafish demonstrated that PKCι catalytic activity is required tissue-autonomously for cardiac and neural progenitor polarity and morphogenesis, extending the polarity function from cultured epithelial cells to in vivo organogenesis.

    Evidence Zebrafish heart-and-soul mutant rescue with catalytic-dead mutant, mosaic analysis, live imaging; spinal cord progenitor division analysis

    PMID:16319113 PMID:19449304

    Open questions at the time
    • In vivo substrates mediating cardiac morphogenesis unknown
    • Whether PKCζ compensates partially in zebrafish not addressed
  7. 2014 High

    Identification of SOX2 as a direct PKCι substrate whose phosphorylation drives HHAT transcription and Hedgehog ligand production revealed the first oncogenic phosphorylation circuit for PKCι, explaining how 3q26 amplification promotes lung squamous cell carcinoma stemness.

    Evidence In vitro kinase assay, ChIP, siRNA, reporter assay, mouse tumor model

    PMID:24525231

    Open questions at the time
    • SOX2 phosphosite(s) not fully mapped
    • Whether this axis operates in non-lung cancers unclear
  8. 2016 Medium

    PRKCI was shown to suppress autophagy via PIK3CA/AKT–mTOR activation, while dominant-negative PRKCI mutants induced autophagy, establishing a kinase activity–dependent regulation of autophagic flux that complemented the polarity and NF-κB branches of PKCι signaling.

    Evidence siRNA knockdown, overexpression, dominant-negative mutants (L485M, P560R), LC3B-II flux assay in U2OS cells

    PMID:26792725

    Open questions at the time
    • Direct mTOR pathway substrate of PKCι not identified
    • Cell-type generalizability not tested beyond U2OS
  9. 2020 High

    Coordinate amplification of PRKCI, SOX2, and ECT2 on 3q26 was shown to be sufficient—with Trp53 loss—to transform mouse lung basal stem cells into LSCC, and PKCι interaction with RIPK2 was found to enhance NF-κB/JNK/ERK signaling in pancreatic cancer, expanding the oncogenic substrate repertoire of PKCι.

    Evidence Mouse basal stem cell transformation, gene expression profiling; Co-IP of PRKCI–RIPK2, xenograft

    PMID:31968252 PMID:37016317

    Open questions at the time
    • ECT2 mechanism downstream of PKCι not molecularly defined
    • RIPK2 phosphosite not mapped
  10. 2022 High

    Conditional pancreatic Prkci knockout demonstrated that PKCι is required for autophagy in acinar cells in vivo and that its loss promotes early neoplasia but blocks adenocarcinoma progression, resolving a context-dependent tumor-suppressive versus oncogenic duality for PKCι.

    Evidence Pancreas-specific Prkci KO mouse, KrasG12D epistasis, P62 aggregation/autophagy marker analysis, caerulein pancreatitis

    PMID:35159064

    Open questions at the time
    • Direct autophagy substrate of PKCι in acinar cells not identified
    • Whether autophagy loss is the sole mechanism blocking PDAC progression unclear
  11. 2025 Medium

    A series of studies identified three new direct PKCι substrates—TGFβR1 (stabilized against proteasomal degradation), c-Myc (Ser21 phosphorylation prevents ubiquitination), and Jak2 (Ser633 phosphorylation activates STAT3/VEGFA)—collectively explaining PKCι's roles in EMT, proliferation, and angiogenesis in colorectal cancer.

    Evidence In vitro kinase assays with site-directed mutagenesis, ubiquitination assays, endothelial tube formation, Prkci KO xenograft models

    PMID:40382656 PMID:40840329 PMID:41188443

    Open questions at the time
    • All three substrates reported by a single group; independent replication needed
    • Structural basis of substrate recognition not determined
    • Relative contribution of each substrate to in vivo tumor phenotype not dissected
  12. 2025 High

    Rare loss-of-function PRKCI variants were identified as a cause of Van der Woude syndrome, with epistasis experiments placing PKCι upstream of IRF6 in the periderm differentiation program required for palatal fusion—the first Mendelian disease linked to PRKCI.

    Evidence Human genetic analysis of de novo variants, zebrafish functional validation of three alleles, phosphomimetic IRF6 rescue

    PMID:40902599

    Open questions at the time
    • Direct phosphorylation of IRF6 by PKCι not demonstrated
    • Genotype-phenotype spectrum across additional VWS families not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full repertoire of direct PKCι substrates in polarity and autophagy contexts, the structural basis for PKCι substrate selectivity versus PKCζ, and whether the recently identified oncogenic substrates (TGFβR1, c-Myc, Jak2) are relevant across cancer types beyond colorectal cancer.
  • No crystal structure of full-length PKCι in complex with a substrate
  • Isoform-specific (ι vs. ζ) substrate selectivity mechanism unknown
  • Therapeutic window for PKCι inhibition in cancer vs. normal polarity not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 6 GO:0140096 catalytic activity, acting on a protein 6
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 6 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 2
Partners
CDC42IKBKBPARD3PARD6BRIPK1RIPK2SOX2SQSTM1
Complex memberships
PAR3–PAR6–aPKC polarity complexp62–RIP–aPKC NF-κB signaling complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 PKC iota (PRKCI) was molecularly cloned and characterized as a novel atypical PKC isoform. It encodes a 587-amino acid serine-threonine kinase with greatest homology to PKC zeta (72% overall, 84% in catalytic domain), contains a conserved pseudosubstrate sequence, lacks a Ca2+-binding region, and has only one cysteine-rich zinc finger-like domain. Stable expression in CHO-K1 cells showed a 65 kDa protein with increased kinase activity toward myelin basic protein. cDNA cloning, Northern blot, Western blot, in vitro kinase assay The Journal of biological chemistry High 8226978
1996 The product of the pro-apoptotic par-4 gene specifically interacts with the regulatory domains of atypical PKC isoforms (zeta PKC and lambda/iota PKC), dramatically inhibiting their enzymatic activity. Cotransfection of wild-type (but not kinase-inactive) atypical PKCs abrogated par-4-induced apoptotic morphological changes in NIH-3T3 cells, establishing that atypical PKC activity promotes cell survival downstream of par-4. Co-immunoprecipitation, in vitro kinase assay, dominant-negative mutagenesis, cell transfection with apoptosis readout Cell High 8797824
1999 Atypical PKC isoforms (lambda/iota PKC and zeta PKC) activate NF-κB through direct binding and phosphorylation of IKKβ (at Ser177 and Ser181), but not IKKα. Dominant-negative lambda/iota PKC impairs RIP-stimulated NF-κB activation. Recombinant active atypical PKC directly phosphorylates IKKβ in vitro, placing atypical PKCs upstream of IKKβ in the TNFα-NF-κB pathway. Co-immunoprecipitation, in vitro kinase assay, dominant-negative transfection, site-directed mutagenesis Molecular and cellular biology High 10022904
1999 The aPKC-binding protein p62 selectively interacts with RIP (but not TRAF2), bridging the atypical PKCs to RIP in the TNFα signaling pathway. This establishes a signaling cascade: TNF-R1→TRADD/RIP/p62/aPKCs/IKKβ for NF-κB activation. Dominant-negative lambda/iota PKC impairs RIP-stimulated NF-κB activation, and antisense p62 severely abrogates NF-κB activation. Co-immunoprecipitation, in vitro binding assay, dominant-negative transfection, antisense knockdown, NF-κB reporter assay The EMBO journal High 10356400
2000 Par6 forms a complex with Cdc42-GTP, a human homologue of PAR-3, and the regulatory domains of atypical PKC (including PKCι). This Par6-Par3-aPKC-Cdc42 complex is required for formation of normal tight junctions at epithelial cell-cell contacts, linking Cdc42 polarity signaling to atypical PKC via Par6 as a key adaptor. Yeast two-hybrid, Co-immunoprecipitation, dominant-negative expression, tight junction permeability assay Nature cell biology High 10934474
2001 Atypical PKC (aPKC, including the iota isoform) is a component of the evolutionarily conserved PAR protein complex (aPKC-ASIP/PAR-3-PAR-6 ternary complex) that localizes to the apical junctional region of MDCK epithelial cells. Overexpression of dominant-negative aPKC causes mislocalization of PAR-3, severely disrupts tight junction biogenesis, increases paracellular ion diffusion, and impairs epithelial apico-basal polarity. Dominant-negative mutagenesis, immunocytochemistry, paracellular diffusion assay, Co-immunoprecipitation The Journal of cell biology High 11257119
2003 The PB1 (Phox and Bem1p) domain mediates interactions between atypical PKCs (lambda/iota and zeta PKC) and scaffold proteins p62 and Par6. Mutation analyses identified critical basic charge cluster residues in aPKC PB1 domains that interact with an acidic loop/helix in p62, establishing molecular basis for aPKC coupling to NF-κB and cell polarity signaling pathways. Mutation analysis, molecular modeling, Co-immunoprecipitation, yeast two-hybrid The Journal of biological chemistry High 12813044
2005 Zebrafish heart and soul (Has)/PRKCi is required tissue-autonomously within the myocardium for normal heart morphogenesis, and this function depends on its catalytic activity. PRKCi and Nok/Mpp5 (Pals1) are required early for polarized epithelial organization and coherence of myocardial cells during heart cone formation, placing PRKCi as essential for apicobasal polarity in cardiac tissue. Genetic rescue (catalytic-dead mutant), tissue-specific mosaic analysis, live imaging, zebrafish mutant phenotype Development (Cambridge, England) High 16319113
2009 In zebrafish spinal cord, loss of PrkCi function causes neural precursor divisions to become oblique during late embryogenesis, resulting in excess oligodendrocyte production and loss of dividing progenitor cells. PrkCi is required for planar cell division orientation and asymmetric self-renewing division of spinal cord precursors, acting through apicobasal polarity maintenance. Time-lapse imaging, zebrafish loss-of-function, cell fate analysis (oligodendrocyte vs. progenitor counting) Developmental dynamics Medium 19449304
2012 The analog-sensitive kinase method was adapted for in vivo use in zebrafish embryos to identify PKCι substrates. Analog-sensitive Prkci uniquely thiophosphorylates substrates using bulky ATPγS analogs, enabling enrichment and identification of kinase substrates by immunoaffinity purification of thiophosphopeptides in the developing embryo. Analog-sensitive kinase/chemical genetics, mass spectrometry, thiophosphopeptide immunoaffinity purification in zebrafish PloS one Medium 22768194
2014 PKCι phosphorylates SOX2 and recruits it to the promoter of Hedgehog acyltransferase (HHAT), the rate-limiting enzyme in Hh ligand production. PKCι-mediated SOX2 phosphorylation is required for HHAT promoter occupancy and HHAT expression, establishing a PKCι-SOX2-HHAT signaling axis that drives a stem-like phenotype in lung squamous cell carcinoma. PRKCI and SOX2 are coamplified on chromosome 3q26. In vitro kinase assay (PKCι phosphorylates SOX2), chromatin immunoprecipitation (promoter occupancy), siRNA knockdown, reporter assay, mouse tumor model Cancer cell High 24525231
2016 PRKCI overexpression impairs functional autophagy in U2OS cells, as evidenced by decreased LC3B-II levels and reduced degradation of autophagic substrates. Conversely, PRKCI knockdown induces autophagy. Two novel dominant-negative PRKCI mutants (L485M and P560R) also induce autophagy. Mechanistically, PRKCI knockdown-mediated autophagy is associated with inactivation of the PIK3CA/AKT-MTOR signaling pathway. siRNA knockdown, overexpression, site-directed mutagenesis, LC3B-II western blot, autophagic flux assay Biochemical and biophysical research communications Medium 26792725
2016 Prkci is required for non-autonomous polarity cue production during cavitation in embryoid bodies. Prkci-null cells fail to properly segregate apical-basal proteins and cannot form a coordinated ectodermal epithelium. When mixed with wildtype cells, cavitation is rescued, indicating Prkci is required to produce (not respond to) non-autonomous polarity cues. Neither BMP4 nor EZRIN overexpression fully rescues the polarized epithelium. Knockout ES cells, chimeric embryoid bodies, live imaging, immunofluorescence, BMP4/EZRIN rescue experiments Developmental biology Medium 27312576
2017 PRKCI promotes immune suppression in ovarian cancer by upregulating TNFα to generate a myeloid-derived suppressor cell-enriched, cytotoxic T-cell-depleted tumor microenvironment. YAP1 was identified as a downstream effector of PRKCI in ovarian tumor progression, establishing a PRKCI-YAP1 signaling axis in immune evasion. Transgenic mouse model, cytokine measurement, immune cell profiling (MDSC/T-cell quantification), siRNA knockdown, system-level analysis Genes & development Medium 28698296
2017 PRKCI is a direct target of miR-29c in dorsal root ganglia neurons. High glucose upregulates miR-29c which reduces PRKCI protein, impairing axonal growth. Knockdown of endogenous miR-29c restores PRKCI protein and axonal growth under high glucose. Knockdown of PRKCI itself under normal glucose inhibits axonal growth, establishing PRKCI as a positive regulator of axonal growth in DRG neurons. Dual-luciferase 3'UTR reporter assay, siRNA knockdown, Western blot, axonal growth measurement in DRG neurons Molecular neurobiology Medium 28070856
2020 Chromosome 3q26 copy number gains occur early in LSCC tumorigenesis and drive coordinate overexpression of PRKCI, SOX2, and ECT2. PRKCI and SOX2 collaborate to activate a transcriptional program enforcing LSCC lineage, while PRKCI and ECT2 collaborate to promote oncogenic growth. Overexpression of all three oncogenes with Trp53 loss transforms mouse lung basal stem cells into histological LSCC. Mouse transformation model (basal stem cell), genomic analysis, gene expression profiling, siRNA knockdown, mouse tumor formation Cell reports High 31968252
2020 PKCι interacts with RIPK2 kinase in pancreatic cancer cells, as demonstrated by co-immunoprecipitation and immunofluorescence. The PRKCI-RIPK2 complex enhances phosphorylation of downstream NF-κB, JNK, and ERK signaling. RIPK2 knockout inhibits subcutaneous tumor growth and liver metastasis of pancreatic cancer and suppresses autophagosome formation while increasing ROS and apoptosis. Co-immunoprecipitation, immunofluorescence, RIPK2 knockout (in vitro and xenograft), phosphorylation analysis by Western blot Molecular medicine (Cambridge, Mass.) Medium 37016317
2022 Pancreas-specific Prkci knockout increases acinar cell DNA damage, apoptosis, immune cell infiltration, and causes P62 aggregation with loss of autophagic vesicles, establishing PKCι as required for pancreatic acinar cell autophagy. Loss of pancreatic Prkci promoted Kras-mediated pancreatic intraepithelial neoplasia formation but blocked progression to adenocarcinoma, consistent with an autophagy-dependent mechanism. Conditional pancreas-specific Prkci knockout mouse, histology, immunostaining for P62/autophagy markers, caerulein pancreatitis model, KrasG12D cancer progression model Cancers High 35159064
2022 A point mutation in Prkci (identified in Tvrm323 mice) acts as a genetic modifier of Crb1-associated retinal dysplasia. Epistasis analysis showed the increased dysplastic phenotype required homozygosity of the Crb1rd8 allele, establishing Prkci as a modifier gene that shapes Crb1-associated retinal disease, likely through its role in apicobasal polarity. Chemical mutagenesis screen, genetic mapping, exome sequencing, epistasis analysis, immunohistology, electroretinography PLoS genetics Medium 35675330
2022 PRKCI mediates radiosensitivity in cervical cancer through the Hedgehog/GLI1 pathway. PRKCI functions downstream of the Hh/GLI1 pathway, phosphorylating and activating transcription factor GLI1. PRKCI knockdown alters GLI1 relocalization and phosphorylation, increasing radiosensitivity, and the PKCι inhibitor auranofin acts as a radiosensitizer in vitro and in vivo. Knockdown/overexpression, colony formation assay, flow cytometry (apoptosis/cell cycle), Western blot, immunofluorescence, xenograft Frontiers in oncology Medium 35785194
2024 PRKCI interacts with SQSTM1/p62 (by co-immunoprecipitation) in osteosarcoma cells. Knockdown of PRKCI inhibits proliferation, migration, invasion, and arrests cell cycle at G2/M, operating through inactivation of the Akt/mTOR signaling pathway. Co-immunoprecipitation, siRNA knockdown, CCK-8, transwell, flow cytometry, Western blot for Akt/mTOR pathway Frontiers in oncology Low 39015499
2025 Rare loss-of-function variants in PRKCI cause Van der Woude syndrome (lower lip pits and orofacial clefts). Functional validation in zebrafish confirmed three alleles (p.Arg130His, p.Asn383Ser, p.Leu385Phe) as loss-of-function. Phosphomimetic IRF6 rescues aPKC inhibition effects, placing PRKCI upstream of IRF6 in the periderm transcriptional regulatory network governing palatal fusion. Zebrafish functional assay (enveloping layer/periderm), genetic analysis of de novo variants, phosphomimetic IRF6 rescue experiment American journal of human genetics High 40902599
2025 The PAR6B-PRKCI-PAR3 polarity complex regulates the cell cycle of type II alveolar epithelial cells (AEC2s). Reduced PAR3-PARD6B-PRKCI complex levels arrest AEC2 cell cycle in the G0-G1 phase, impairing self-proliferation and contributing to abnormal alveolar repair in the emphysema subtype of COPD. Co-immunoprecipitation, mass spectrometry, 3D spheroid formation, viral transfection, cell cycle analysis Stem cell research & therapy Medium 40001200
2025 Prkci phosphorylates and stabilizes TGFβ receptor 1 (Tgfbr1), preventing its proteasomal degradation and amplifying downstream TGF-β signaling cascades in colorectal cancer. This stabilization promotes epithelial-to-mesenchymal transition, migration, and invasion. In vivo, Prkci knockout significantly reduced liver and lung metastases in mouse models. Co-immunoprecipitation, in vitro kinase assay (phosphorylation of Tgfbr1), proteasome inhibitor rescue, EMT marker analysis, Prkci knockout mouse xenograft Cell communication and signaling Medium 40382656
2025 Prkci phosphorylates c-Myc at serine 21, inhibiting its ubiquitin-mediated proteasomal degradation and stabilizing c-Myc protein. The pro-proliferative effect of Prkci in colorectal cancer is dependent on c-Myc S21 phosphorylation. Prkci deletion in mouse models significantly delayed tumor growth and improved survival. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (S21 phosphosite), ubiquitination assay, Prkci knockout mouse tumor model NPJ precision oncology Medium 41188443
2025 Prkci promotes tumor angiogenesis in colorectal cancer by phosphorylating Jak2 at serine 633, leading to downstream Stat3 activation and increased Vegfa expression. In vitro, Prkci overexpression enhanced endothelial cell proliferation, migration, and tube formation. Prkci knockout in CRC cells significantly reduced tumor growth and angiogenesis in vivo. In vitro kinase assay (Jak2 S633 phosphorylation), endothelial cell functional assays (proliferation, migration, tube formation), Prkci knockout xenograft Neoplasia (New York, N.Y.) Medium 40840329
2024 Neural progenitor-specific ablation of both Prkci and Prkcz aPKC paralogs in mouse brain reveals a critical developmental window wherein aPKC kinase function is indispensable for neurodevelopment. A kinase-inactive PRKCI knock-in confirms that catalytic activity is required during this window. Outside this period, loss of both aPKCs causes unexpectedly mild effects. Conditional knockout mice (neural stem cells, neurons, astrocytes, NG2+ cells), kinase-inactive knock-in, gross brain morphology and viability assessment bioRxivpreprint Medium

Source papers

Stage 0 corpus · 97 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nature cell biology 761 10934474
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2013 Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Science signaling 383 24255178
2001 Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. The Journal of cell biology 378 11257119
1999 The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. The EMBO journal 344 10356400
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1996 The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C. Cell 325 8797824
2003 Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins. The Journal of biological chemistry 322 12813044
1999 Activation of IkappaB kinase beta by protein kinase C isoforms. Molecular and cellular biology 310 10022904
1993 Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells. The Journal of biological chemistry 310 8226978
2006 A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 302 16678097
2019 Intrinsically Disordered Protein TEX264 Mediates ER-phagy. Molecular cell 296 31006538
2014 The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma. Cancer cell 250 24525231
2020 circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway. Molecular cancer 142 33234130
2002 Stability of a PKCI-1-related mRNA is controlled by the splicing factor ASF/SF2: a novel function for SR proteins. Genes & development 120 11877379
2000 Wpkci, encoding an altered form of PKCI, is conserved widely on the avian W chromosome and expressed in early female embryos: implication of its role in female sex determination. Molecular biology of the cell 113 11029061
2017 PRKCI promotes immune suppression in ovarian cancer. Genes & development 78 28698296
2005 Heart and soul/PRKCi and nagie oko/Mpp5 regulate myocardial coherence and remodeling during cardiac morphogenesis. Development (Cambridge, England) 71 16319113
2008 Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma. Genes, chromosomes & cancer 64 17990328
1998 Characterization of PKCI and comparative studies with FHIT, related members of the HIT protein family. Experimental cell research 62 9770345
2009 Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level. BMC neuroscience 54 19912621
2006 RGSZ1 interacts with protein kinase C interacting protein PKCI-1 and modulates mu opioid receptor signaling. Cellular signalling 52 17126529
2000 Interactions of Cdk7 and Kin28 with Hint/PKCI-1 and Hnt1 histidine triad proteins. The Journal of biological chemistry 52 10958787
2017 miR-217-5p induces apoptosis by directly targeting PRKCI, BAG3, ITGAV and MAPK1 in colorectal cancer cells. Journal of cell communication and signaling 49 28905214
2019 Circular RNA circ-PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-3680-3p in esophageal squamous cell carcinoma. Journal of cellular biochemistry 45 30659640
2008 Distribution and expression of protein kinase C interactive protein (PKCI/HINT1) in mouse central nervous system (CNS). Neurochemical research 41 18270824
2020 Chromosome 3q26 Gain Is an Early Event Driving Coordinated Overexpression of the PRKCI, SOX2, and ECT2 Oncogenes in Lung Squamous Cell Carcinoma. Cell reports 32 31968252
2020 Circular RNA PRKCI silencing represses esophageal cancer progression and elevates cell radiosensitivity through regulating the miR-186-5p/PARP9 axis. Life sciences 31 32739469
2019 Circular RNA PRKCI promotes glioma cell progression by inhibiting microRNA-545. Cell death & disease 30 31409777
2017 MiR-29c/PRKCI Regulates Axonal Growth of Dorsal Root Ganglia Neurons Under Hyperglycemia. Molecular neurobiology 30 28070856
2020 Addiction to protein kinase Cɩ due to PRKCI gene amplification can be exploited for an aptamer-based targeted therapy in ovarian cancer. Signal transduction and targeted therapy 28 32820156
2021 circ-PRKCI targets miR-1294 and miR-186-5p by downregulating FOXK1 expression to suppress glycolysis in hepatocellular carcinoma. Molecular medicine reports 26 33880589
2019 Role and mechanism of circ-PRKCI in hepatocellular carcinoma. World journal of gastroenterology 24 31086464
1996 Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1). Genomics 24 8812426
2018 Down-regulation of circ-PRKCI inhibits cell migration and proliferation in Hirschsprung disease by suppressing the expression of miR-1324 target PLCB1. Cell cycle (Georgetown, Tex.) 23 29895226
2021 Silencing circRNA protein kinase C iota (circ-PRKCI) suppresses cell progression and glycolysis of human papillary thyroid cancer through circ-PRKCI/miR-335/E2F3 ceRNA axis. Endocrine journal 20 33716239
1992 Purification of PKC-I, an endogenous protein kinase C inhibitor, and types II and III protein kinase C isoenzymes from human neutrophils. The Biochemical journal 19 1599424
2022 Tumor Cell-Derived Exosomal circ-PRKCI Promotes Proliferation of Renal Cell Carcinoma via Regulating miR-545-3p/CCND1 Axis. Cancers 18 36612120
2014 miR-219 inhibits the growth and metastasis of TSCC cells by targeting PRKCI. International journal of clinical and experimental medicine 18 25356169
2001 Effect of protein kinase C inhibitor (PKCI) on radiation sensitivity and c-fos transcription. International journal of radiation oncology, biology, physics 18 11173133
2023 Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-κB/JNK/ERK phosphorylation. Molecular medicine (Cambridge, Mass.) 17 37016317
2016 PRKCI negatively regulates autophagy via PIK3CA/AKT-MTOR signaling. Biochemical and biophysical research communications 17 26792725
2015 Association of polymorphisms in PRKCI gene and risk of prostate cancer in a sample of Iranian Population. Cellular and molecular biology (Noisy-le-Grand, France) 17 26475383
2017 Intratumoral Heterogeneity of Somatic Mutations for NRIP1, DOK1, ULK1, ULK2, DLGAP3, PARD3 and PRKCI in Colon Cancers. Pathology oncology research : POR 15 28844109
2017 Integrated genomic analysis of clear cell ovarian cancers identified PRKCI as a potential therapeutic target. Oncotarget 15 29228547
2022 Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice. Cancers 14 35159064
2020 Circular RNA PRKCI and microRNA-545 relate to sepsis risk, disease severity and 28-day mortality. Scandinavian journal of clinical and laboratory investigation 14 32985287
2019 Circular RNA circ-PRKCI promotes cell proliferation and invasion by binding to microRNA-545 in gastric cancer. European review for medical and pharmacological sciences 13 31773680
2006 PKCI-W forms a heterodimer with PKCI-Z and inhibits the biological activities of PKCI-Z in vitro, supporting the predicted role of PKCI-W in sex determination in birds. Journal of biochemistry 13 16428323
2022 Impact of deleterious missense PRKCI variants on structural and functional dynamics of protein. Scientific reports 12 35260606
2021 Circ-PRKCI Alleviates Lipopolysaccharide-induced Human Kidney 2 Cell Injury by Regulating miR-106b-5p/GAB1 Axis. Journal of cardiovascular pharmacology 12 34269703
2022 Identification of Arhgef12 and Prkci as genetic modifiers of retinal dysplasia in the Crb1rd8 mouse model. PLoS genetics 11 35675330
2009 Apical polarity protein PrkCi is necessary for maintenance of spinal cord precursors in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 10 19449304
2022 PRKCI Mediates Radiosensitivity via the Hedgehog/GLI1 Pathway in Cervical Cancer. Frontiers in oncology 9 35785194
2020 The interplay between PRKCI/PKCλ/ι, SQSTM1/p62, and autophagy orchestrates the oxidative metabolic response that drives liver cancer. Autophagy 9 32686580
2012 In vivo conditions to identify Prkci phosphorylation targets using the analog-sensitive kinase method in zebrafish. PloS one 9 22768194
2014 Two novel PRKCI polymorphisms and prostate cancer risk in an Eastern Chinese Han population. Molecular carcinogenesis 6 24510606
2024 miR-630 as a therapeutic target in pancreatic cancer stem cells: modulation of the PRKCI-Hedgehog signaling axis. Biology direct 5 39529141
2020 Circular RNA circ-PRKCI promotes lung cancer progression by binding to microRNA-1324 to regulate MECP2 expression. European review for medical and pharmacological sciences 5 33155212
2024 Circular RNA PRKCI (hsa_circ_0067934): a potential target in the pathogenesis of human malignancies. Frontiers in oncology 4 38741779
2024 Downregulation of PRKCI inhibits osteosarcoma cell growth by inactivating the Akt/mTOR signaling pathway. Frontiers in oncology 4 39015499
2001 The assignment of PRKCI to bovine chromosome 1q34-->q36 by FISH suggests a new assignment to human chromosome 3. Cytogenetics and cell genetics 4 11978974
1999 HIT family genes: FHIT but not PKCI-1/HINT produces altered transcripts in colorectal cancer. British journal of cancer 4 10555761
2025 Has_circRNA_0122683 (circ-PRKCI) relieves ferroptosis of HPAEpiCs in sepsis-induced acute lung injury by sponging miR-382-5p. PeerJ 3 40386233
2023 Investigation of UTR Variants by Computational Approaches Reveal Their Functional Significance in PRKCI Gene Regulation. Genes 3 36833174
2021 Immunosurveillance, interferon, and autophagic networking in cancer: the PRKCI-ULK2 paradigm. Autophagy 3 34895031
2025 MK886 ameliorates Alzheimer's disease by activating the PRKCI/AKT signaling pathway. European journal of pharmacology 2 39922422
2025 The PAR6B-PRKCI-PAR3 complex influences alveolar regeneration in patients with the emphysema subtype of chronic obstructive pulmonary disease. Stem cell research & therapy 2 40001200
2025 Unravelling the role of PRKCI and key-cancer related genes in breast cancer development and metastasis. Discover oncology 2 40100546
2025 Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy. American journal of human genetics 2 40902599
2016 Prkci is required for a non-autonomous signal that coordinates cell polarity during cavitation. Developmental biology 2 27312576
2025 Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy. medRxiv : the preprint server for health sciences 1 39867391
2025 Prkci promotes colorectal cancer metastasis by phosphorylating and stabilizing Tgfbr1 to activate TGF-β signaling. Cell communication and signaling : CCS 1 40382656
2026 Circ-PRKCI attenuates acute lung injury secondary to sepsis by targeting the miR-106b-5p/GAB1 axis. European journal of medical research 0 41530882
2026 Correction: PRKCI mediates radiosensitivity via the Hedgehog/GLI1 pathway in cervical cancer. Frontiers in oncology 0 41608557
2025 Correction: Downregulation of PRKCI inhibits osteosarcoma cell growth by inactivating the Akt/mTOR signaling pathway. Frontiers in oncology 0 40692866
2025 Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis: Short Name: Prkci in tumor angiogenesis. Neoplasia (New York, N.Y.) 0 40840329
2025 Prkci acts a pro-proliferation factor in colorectal cancer. NPJ precision oncology 0 41188443
2022 Author Correction: Circular RNA circ-PRKCI promotes cell proliferation and invasion by binding to microRNA-545 in gastric cancer. European review for medical and pharmacological sciences 0 35113408