Translocation of PKC theta to plasma membrane

Stable Identifier
R-HSA-202328
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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DAG along with intracellular calcium signals cooperatively to activate PKCs, which then trigger other pathways such as the NF-kB pathway, ultimately leading to mast cell (MC) degranulation and cytokine production (Wu 2011). PKC theta is a member of the Ca++ independent and DAG dependent, novel PKC subfamily expressed mainly in T cells. It contains, N-term C2 like domain, a pseudosubstrate (PS), DAG binding (C1) domain and a C-term kinase domain. The PS sequence resembles an ideal substrate with the exception that it contains an alanine residue instead of a substrate serine residue, is bound to the kinase domain in the resting state. As a result, PKC theta is maintained in a closed inactive state, which is inaccessible to cellular substrates.
MCs express several Protein kinase C (PKC) isozymes and these kinases are involved in both the activation and termination of the degranulation process. PKC-delta is a negative regulator of FCERI mediated mast cell degranulation, whereas PKC-theta facilitates in degranulation (Leitges et al. 2002, Liu et al. 2001). In response to FCERI activation PKC-theta translocates to membrane by binding to DAG with its C1 domain. PKC-theta exists in two conformations closed/inactive and open/active state. In resting state, PKC-theta is autoinhibited where the pseudosubstrate sequence in the N-terminal regulatory region of PKC-theta forms intramolecular interaction with the substrate-binding region in the catalytic domain. This prevents the catalytic domain gaining access to substrates. The allosteric change of PKC-theta from closed to open state involves two important mechanisms: DAG binding to the C1 domains and autophosphorylation of T538 on the activation loop. Interaction with DAG induces conformational change resulting in the exposure of the activation loop of PKC-theta (Wang et al. 2012, Melowic et al. 2007).

Literature References
PubMed ID Title Journal Year
17548359 Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Ctheta

Melowic, HR, Stahelin, RV, Blatner, NR, Tian, W, Hayashi, K, Altman, A, Cho, W

J. Biol. Chem. 2007
16978534 Selective function of PKC-theta in T cells

Manicassamy, S, Gupta, S, Sun, Z

Cell Mol Immunol 2006
12473184 Protein kinase C-theta (PKC theta): a key enzyme in T cell life and death

Altman, A, Villalba, M

J Biochem (Tokyo) 2002
11358993 Protein kinase C theta is expressed in mast cells and is functionally involved in Fcepsilon receptor I signaling

Liu, Y, Graham, C, Parravicini, V, Brown, MJ, Rivera, J, Shaw, S

J. Leukoc. Biol. 2001
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