Protein kinase C iota type
Also known as: DXS1179E, PRKCI
Function
Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity).
Classification
- Family (Pfam)
- PF00130 C1_1, PF00564 PB1, PF00069 Pkinase, PF00433 Pkinase_C
- InterPro
- AGC-kinase_C, aPKC_iota, C1-like_sf, DAG/PE-bd, Kinase-like_dom_sf, PB1-like, PB1_aPKC, PB1_dom, PKC, PKC_DAG/PE, Pkinase_C, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
- Functional cluster
- Serine/Threonine Protein Kinases
Experimental structures · PDB · 15
- 1VD2 NMR
- 1WMH X-ray 1.50A
- 1ZRZ X-ray 3.00A
- 3A8W X-ray 2.10A
- 3A8X X-ray 2.00A
- 3ZH8 X-ray 2.74A
- 5LI1 X-ray 2.00A
- 5LI9 X-ray 1.79A
- 5LIH X-ray 3.25A
- 6ILZ X-ray 3.26A
- 8R3X X-ray 2.59A
- 8R3Y EM 3.68A
- … and 3 more
A predicted model is available from AlphaFold.
Gene Ontology · 49
- GO:0016324 apical plasma membrane
- GO:0005923 bicellular tight junction
- GO:0005903 brush border
- GO:0031252 cell leading edge
- GO:0005929 cilium
- GO:0005829 cytosol
- GO:0005768 endosome
- GO:0070062 extracellular exosome
- GO:0098978 glutamatergic synapse
- GO:0000139 Golgi membrane
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0098685 Schaffer collateral - CA1 synapse
- GO:0043220 Schmidt-Lanterman incisure
- GO:0070160 tight junction
- GO:0005524 ATP binding
- GO:0004699 diacylglycerol-dependent, calcium-independent serine/threonine kinase activity
- GO:0005543 phospholipid binding
- GO:0004672 protein kinase activity
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0008270 zinc ion binding
- GO:0016477 cell migration
- GO:0045216 cell-cell junction organization
- GO:0062197 cellular response to chemical stress
- GO:0032869 cellular response to insulin stimulus
- GO:0007010 cytoskeleton organization
- GO:0030010 establishment of cell polarity
- GO:0045197 establishment or maintenance of epithelial cell apical/basal polarity
- GO:0048194 Golgi vesicle budding
- GO:0035556 intracellular signal transduction
- GO:0061024 membrane organization
- GO:0043066 negative regulation of apoptotic process
- GO:0034351 negative regulation of glial cell apoptotic process
- GO:0043524 negative regulation of neuron apoptotic process
- GO:0046326 positive regulation of D-glucose import across plasma membrane
- GO:2000353 positive regulation of endothelial cell apoptotic process
- GO:0060252 positive regulation of glial cell proliferation
- GO:0010976 positive regulation of neuron projection development
- GO:0045747 positive regulation of Notch signaling pathway
- GO:1903078 positive regulation of protein localization to plasma membrane
- GO:0072659 protein localization to plasma membrane
- GO:0006468 protein phosphorylation
- GO:0006612 protein targeting to membrane
- GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels
- GO:0070555 response to interleukin-1
- GO:0046903 secretion
- GO:0016192 vesicle-mediated transport
Drugs targeting this protein · 5
- GSK-690693 inhibitor
- SOTRASTAURIN inhibitor
- UCN-01 inhibitor
- CEP-2563 DIHYDROCHLORIDE inhibitor
- MIDOSTAURIN inhibitor
Related proteins · sequence + function similarity
- Protein kinase C iota type 1.00
- Protein kinase C iota type 1.00
- Protein kinase C iota type 1.00
- Protein kinase C iota type 0.99
- Protein kinase C zeta type 0.96
- Protein kinase C zeta type 0.96
- Protein kinase C zeta type 0.96
- Protein kinase C zeta type 0.96
- Protein kinase C-like 3 0.96
- Protein kinase C-like 3 0.95
- Atypical protein kinase C 0.94
- Protein kinase C-like 1B 0.84
Co-cited proteins · studied together in the literature
- Partitioning defective 6 homolog alpha 4 shared papers
- Protein ECT2 2 shared papers
- Ras-related protein Rab-2A 1 shared papers
- Protein kinase C iota type 1 shared papers
- Serine/threonine-protein kinase SMG1 2 shared papers
- Sequestosome-1 1 shared papers
- Ezrin 1 shared papers
- Partitioning defective 6 homolog beta 2 shared papers
- Glyceraldehyde-3-phosphate dehydrogenase 1 shared papers
- Protein kinase C zeta type 6 shared papers
- Lethal(2) giant larvae protein homolog 1 1 shared papers
- Cyclin-dependent kinase 7 1 shared papers
Literature · 43 cited papers
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- PKC-? promotes glioblastoma cell survival by phosphorylating and inhibiting BAD through a phosphatidylinositol 3-kinase pathway. Biochim. Biophys. Acta · 2011
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated phosphorylation. J. Biol. Chem. · 2011
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
- Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular transformation. Oncogene · 2009
- Protein kinase C iota mediates lipid-induced apoptosis of human coronary artery endothelial cells. Microvasc. Res. · 2009
- Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
- A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
- … and 31 more in the literature graph