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PKC iota

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 (PI3K) 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

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Stem Cell>>Wnt Signaling Pathway>>Non-Canonical Wnt Pathway>>PKC iota

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Enzyme>>Protein Kinase>>Intracellular Kinase>>Protein Kinase C (PKC)>>PKC iota

Signal Transduction>>Wnt Signaling Pathway>>Non-Canonical Wnt Pathway>>PKC iota

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>Protein Kinase C (PKC)>>PKC iota

PKC iota Related Pathways

PKC iota Alternative Names

PKC iota, PRKCI, PRKC-lambda/iota, aPKC-lambda/iota, DXS1179E, MGC26534, PKCI, nPKC-iota [Homo sapiens]

PKC iota, Prkci, aPKC-lambda/iota, nPKC-iota, 2310021H13Rik, AI427505, KIAA4165, PKClambda, Pkci, Pkcl, Prkcl, aPKClambda, mKIAA4165 [Mus musculus]

Summaries for PKC iota

Entrez Gene summary for PKC iota:

This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X

OMIM - description for PKC iota:

Sequencing by Mazzarella et al. (1995) demonstrated that the cDNA of PRKCI encodes a 587-amino acid protein with a relative molecular mass of 6,258 kD. A GenBank search revealed that a similar human cDNA sequence had been identified as an iota isoform of protein kinase C. Northern blot analysis detected expression of PRKCI RNA species at high levels in kidney, muscle, lung, and brain, moderate levels in pancreas and placenta, and low levels in heart. De Donato et al. (2001) identified 2 bovine BAC clones containing the PRKCI gene. The sequences from the clones were identical and showed a high degree of identity to the mRNA for the human, rat, and mouse PRKCI genes.

Wikipedia summary for PKC iota:

Protein kinase C iota type is an enzyme that in humans is encoded by the PRKCI gene.This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises at least eight members, which are differentially expressed and are involved in a wide variety of cellular processes. This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbolesters or diacylglycerol. This kinase can be recruited to vesicle tubular clusters (VTCs) by direct interaction with the small GTPase RAB2, where this kinase phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPD/GAPDH) and plays a role in microtubule dynamics in the early secretory pathway. This kinase is found to be necessary for BCL-ABL-mediated resistance to drug-induced apoptosis and therefore protects leukemia cells against drug-induced apoptosis. There is a single exon pseudogene mapped on chromosome X

Human PKC iota Protein General Information

 

Protein names

Recommended name: Protein kinase C iota type EC=2.7.11.13 Alternative name(s): Atypical protein kinase C-lambda/iota Short name=PRKC-lambda/iota Short name=aPKC-lambda/iota nPKC-iota

Sequence length

596 AA.

Domain

The OPR domain mediates interaction with SQSTM1 By similarity. The C1 domain does not bind diacylglycerol (DAG).

Sequence similarities:

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 OPR domain. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain.

Post-translational modification:

On neuronal growth factor (NGF) stimulation, phosphorylated by SRC at Tyr-265, Tyr-280 and Tyr-334. Phosphorylation at Tyr-265 facilitates binding to KPNB1/importin-beta regulating entry of PRKCI into the nucleus. Phosphorylation on Tyr-334 is important for NF-kappa-B stimulation

Subunit structure

Forms a complex with SQSTM1 and MP2K5 By similarity. Interacts directly with SQSTM1 Probable. Interacts with IKBKB. Interacts with PARD6A, PARD6B and PARD6G. Part of a quaternary complex containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) and a GTPase protein (CDC42 or RAC1). Part of a complex with LLGL1 and PARD6B. Interacts with ADAP1/CENTA1. Interaction with SMG1, through the ZN-finger domain, activates the kinase activity. Interacts with CDK7. Forms a complex with RAB2A and GAPDH involved in recruitment onto the membrane of vesicular tubular clusters (VTCs). Interacts with ECT2 ('Thr-359' phosphorylated form). Interacts with PARD6A.

Subcellular location: Cytoplasm. Membrane. Endosome. Nucleus. Note: Transported into the endosome through interaction with SQSTM1/p62. After phosphorylation by SRC, transported into the nucleus through interaction with KPNB1. Colocalizes with CDK7 in the cytoplasm and nucleus. Transported to vesicular tubular clusters (VTCs) through interaction with RAB2A.
Tissue specificity

Predominantly expressed in lung and brain, but also expressed at lower levels in many tissues including pancreatic islets. Highly expressed in non-small cell lung cancers

General information above from UniProt

Function for PKC iota Protein

UniProtKB:

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 (PI3K) 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

Genatlas:

  • PKC iota is involved in the secretory response to nutrients
  • PKC iota plays an essential role for protein transport in the early secretory pathway and required to promote RAB2-mediated vesicle budding at a vesicular tubular clusters subcompartment enriched in recycling cargo
  • PKC iota might play a compensatory role in TCR/CD28-induced signaling
  • indirect co-regulator of HSF1 activity and the heat shock response
  • PKC iota regulates primary dendrite specification of cerebellar Purkinje cells by localizing Golgi apparatus
  • PARD6B and PRKCI control mitotic spindle orientation in polarized epithelia and, furthermore, that PRKCI coordinately regulates multiple processes to promote morphogenesis
  • PKC iota functions with CDC42 and PARD6B to control apical surface positioning
  • PKC iota promotes proper spindle orientation through the phosphorylation of downstream substrates, and promotes cell survival in a kinase-dependent manner
  • expression of PRKCZ and PRKCI or both are dispensable for primitive and adult hematopoietic stem cell fate determination in steady-state and stress hematopoiesis
  • PKC iota phosphorylates ROCK1 and suppresses its junctional localization, thereby allowing cells to retain normally shaped apical domains

Homology for human PKC iota

  • homolog to C.elegans f09es.1
  • homolog to prkcl
  • homolog to PRKCZ

Phenotype Information for PKC iota

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