The Function of PRKCZ
Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro (PubMed:17313651).
Protein names
Recommended name:
Protein kinase C zeta typeAlternative name(s):
nPKC-zeta- RS3753242 (PRKCZ) ??
- RS425277 (PRKCZ) ??
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Top Gene-Substance Interactions
PRKCZ Interacts with These Diseases
Disease | Score |
Substances That Increase PRKCZ
Substances | Interaction | Organism | Category |
Substances That Decrease PRKCZ
Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Expressed in brain, and to a lesser extent in lung, kidney and testis.
Gene Pathways:
Enzyme Regulation:
Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator.
Molecular Function:
- Atp Binding
- Insulin Receptor Substrate Binding
- Metal Ion Binding
- Potassium Channel Regulator Activity
- Protein Kinase C Activity
- Protein Serine/Threonine Kinase Activity
Biological Processes:
- Actin Cytoskeleton Reorganization
- Activation Of Phospholipase D Activity
- Activation Of Protein Kinase B Activity
- Establishment Of Cell Polarity
- Inflammatory Response
- Insulin Receptor Signaling Pathway
- Long-Term Memory
- Long-Term Synaptic Potentiation
- Membrane Depolarization
- Membrane Hyperpolarization
- Microtubule Cytoskeleton Organization
- Negative Regulation Of Apoptotic Process
- Negative Regulation Of Hydrolase Activity
- Negative Regulation Of Insulin Receptor Signaling Pathway
- Negative Regulation Of Peptidyl-Tyrosine Phosphorylation
- Neuron Projection Extension
- Peptidyl-Serine Phosphorylation
- Positive Regulation Of Cell-Matrix Adhesion
- Positive Regulation Of Cell Proliferation
- Positive Regulation Of Erk1 And Erk2 Cascade
- Positive Regulation Of Excitatory Postsynaptic Potential
- Positive Regulation Of Glucose Import
- Positive Regulation Of Insulin Receptor Signaling Pathway
- Positive Regulation Of Interleukin-10 Secretion
- Positive Regulation Of Interleukin-13 Secretion
- Positive Regulation Of Interleukin-4 Production
- Positive Regulation Of Interleukin-5 Secretion
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Positive Regulation Of T-Helper 2 Cell Cytokine Production
- Positive Regulation Of T-Helper 2 Cell Differentiation
- Protein Heterooligomerization
- Protein Kinase C Signaling
- Protein Localization To Plasma Membrane
- Protein Phosphorylation
- Signal Transduction
- Transforming Growth Factor Beta Receptor Signaling Pathway
- Vesicle Transport Along Microtubule