PRKCQ
Description
The PRKCQ (protein kinase C theta) is a protein-coding gene located on chromosome 10.
PRKCQ gene encodes for Protein kinase C theta (PKC-θ), a member of the serine/threonine kinases family, mainly expressed in hematopoietic cells with high levels in platelets and T lymphocytes. PKC-θ plays a role in signal transduction, particularly in T cell activation. Different T cell subpopulations vary in their PKC-θ requirements, making it a potential target for inhibitors in immunotherapy. PKC-θ is a calcium-independent and phospholipid-dependent protein kinase, essential for T-cell activation.
PRKCQ, also known as nPKC-theta, is a calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase. It plays essential roles in T-cell receptor (TCR) signaling, including T-cell activation, proliferation, differentiation, and survival. PRKCQ mediates activation of multiple transcription factors like NF-kappa-B, JUN, NFATC1, and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, PRKCQ is required for the activation of NF-kappa-B and JUN, which are essential for IL2 production. PRKCQ also participates in calcium-dependent NFATC1 and NFATC2 transactivation. PRKCQ activates the canonical NF-kappa-B pathway (NFKB1) by directly phosphorylating CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which activates the IKK complex, resulting in nuclear translocation and activation of NFKB1. PRKCQ may also indirectly activate the non-canonical NF-kappa-B (NFKB2) pathway. PRKCQ phosphorylates the mediator STK39/SPAK in the signaling pathway leading to JUN activation, potentially bypassing MAP kinases signaling. It plays a crucial role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by regulating reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28, PRKCQ can phosphorylate CBLB, which is required for the ubiquitination and subsequent degradation of CBLB, a prerequisite for TCR activation. During T-cell differentiation, PRKCQ plays a significant role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses. It is also necessary for the activation of IL17-producing Th17 cells in the development of inflammatory autoimmune diseases. PRKCQ may play a minor role in Th1 responses. Upon TCR stimulation, PRKCQ mediates T-cell protective survival signals by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, PRKCQ regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1, and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. PRKCQ may relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. PRKCQ may mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. It phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. PRKCQ phosphorylates PDPK1 at 'Ser-504' and 'Ser-532', negatively regulating its ability to phosphorylate PKB/AKT1. PRKCQ phosphorylates CCDC88A/GIV, inhibiting its guanine nucleotide exchange factor activity. PRKCQ is part of a lipid raft complex containing BCL10, CARD11, MALT1, and IKBKB. PRKCQ interacts with GLRX3 (via its N-terminus), ECT2, and CCDC88A/GIV. The interaction with CCDC88A/GIV leads to the phosphorylation of CCDC88A and inhibition of its guanine nucleotide exchange factor activity. PRKCQ also interacts with PRKCH upstream open reading frame 2, leading to inhibition of kinase activity. Finally, PRKCQ interacts with CD28.
PRKCQ is also known as PRKCT, nPKC-theta.
