Target General Infomation
Target ID
T72295
Former ID
TTDR01402
Target Name
mRNA of Protein kinase C-theta
Gene Name
PRKCQ
Synonyms
PRKCQ (mRNA); nPKC-theta (mRNA); PRKCQ
Target Type
Research
Disease Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Function
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non- redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiationand survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-Band JUN, which in turn are essential for IL2 production, and participates to the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non- canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal 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, 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. 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. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1.
BioChemical Class
Kinase
Target Validation
T72295
UniProt ID
EC Number
EC 2.7.11.13
Sequence
MSPFLRIGLSNFDCGSCQSCQGEAVNPYCAVLVKEYVESENGQMYIQKKPTMYPPWDSTF
DAHINKGRVMQIIVKGKNVDLISETTVELYSLAERCRKNNGKTEIWLELKPQGRMLMNAR
YFLEMSDTKDMNEFETEGFFALHQRRGAIKQAKVHHVKCHEFTATFFPQPTFCSVCHEFV
WGLNKQGYQCRQCNAAIHKKCIDKVIAKCTGSAINSRETMFHKERFKIDMPHRFKVYNYK
SPTFCEHCGTLLWGLARQGLKCDACGMNVHHRCQTKVANLCGINQKLMAEALAMIESTQQ
ARCLRDTEQIFREGPVEIGLPCSIKNEARPPCLPTPGKREPQGISWESPLDEVDKMCHLP
EPELNKERPSLQIKLKIEDFILHKMLGKGSFGKVFLAEFKKTNQFFAIKALKKDVVLMDD
DVECTMVEKRVLSLAWEHPFLTHMFCTFQTKENLFFVMEYLNGGDLMYHIQSCHKFDLSR
ATFYAAEIILGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENMLGDAKTNTFC
GTPDYIAPEILLGQKYNHSVDWWSFGVLLYEMLIGQSPFHGQDEEELFHSIRMDNPFYPR
WLEKEAKDLLVKLFVREPEKRLGVRGDIRQHPLFREINWEELERKEIDPPFRPKVKSPFD
CSNFDKEFLNEKPRLSFADRALINSMDQNMFRNFSFMNPGMERLIS
Inhibitor 4-(1H-indol-5-ylamino)-5-styrylnicotinonitrile Drug Info [530390]
4-(1H-indol-5-yloxy)-5-styrylnicotinonitrile Drug Info [530390]
4-(1H-indol-6-ylamino)-5-styrylnicotinonitrile Drug Info [530390]
4-(3H-indol-4-ylamino)-5-styrylnicotinonitrile Drug Info [530390]
8-Octyl-benzolactam-V9 Drug Info [528158]
PROSTRATIN Drug Info [527606]
Pathways
KEGG Pathway NF-kappa B signaling pathway
Vascular smooth muscle contraction
Tight junction
T cell receptor signaling pathway
Inflammatory mediator regulation of TRP channels
Adipocytokine signaling pathway
Measles
PANTHER Pathway Alzheimer disease-amyloid secretase pathway
Angiogenesis
Apoptosis signaling pathway
EGF receptor signaling pathway
Endothelin signaling pathway
FGF signaling pathway
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
Muscarinic acetylcholine receptor 1 and 3 signaling pathway
T cell activation
VEGF signaling pathway
Wnt signaling pathway
5HT2 type receptor mediated signaling pathway
Histamine H1 receptor mediated signaling pathway
Oxytocin receptor mediated signaling pathway
Thyrotropin-releasing hormone receptor signaling pathway
CCKR signaling map ST
Pathway Interaction Database Endothelins
TCR signaling in na&amp
#xef
ve CD4+ T cells
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
TCR signaling in na&amp
ve CD8+ T cells
Thromboxane A2 receptor signaling
Role of Calcineurin-dependent NFAT signaling in lymphocytes
Downstream signaling in na&amp
Reactome Apoptotic cleavage of cellular proteins
Effects of PIP2 hydrolysis
Inactivation, recovery and regulation of the phototransduction cascade
FCERI mediated NF-kB activation
G alpha (z) signalling events
WikiPathways TCR Signaling Pathway
Calcium Regulation in the Cardiac Cell
Insulin Signaling
Wnt Signaling Pathway
Wnt Signaling Pathway and Pluripotency
G Protein Signaling Pathways
Myometrial Relaxation and Contraction Pathways
Fc epsilon receptor (FCERI) signaling
Corticotropin-releasing hormone
Signaling Pathways in Glioblastoma
miRs in Muscle Cell Differentiation
TCR signaling
Netrin-1 signaling
GPCR downstream signaling
Effects of PIP2 hydrolysis
Apoptotic execution phase
References
Ref 527606J Med Chem. 1992 May 29;35(11):1978-86.A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1.
Ref 528158J Med Chem. 2006 May 4;49(9):2681-8.Design and synthesis of 8-octyl-benzolactam-V9, a selective activator for protein kinase C epsilon and eta.
Ref 530390Bioorg Med Chem Lett. 2009 Oct 15;19(20):5829-32. Epub 2009 Aug 29.First generation 5-vinyl-3-pyridinecarbonitrile PKCtheta inhibitors.
Ref 549624US patent application no. 6,190,869, Antisense inhibition of protein kinase C-theta expression.

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