The autoinhibitory C-terminal SH2 domain of phospholipase C-γ2 stabilizes B cell receptor signalosome assembly.

ABSTRACT: The binding of antigen to the B cell receptor (BCR) stimulates the assembly of a signaling complex (signalosome) composed initially of the kinases Lyn, spleen tyrosine kinase (Syk), and Bruton's tyrosine kinase (Btk), as well as the adaptor protein B cell linker (BLNK). Together, these proteins recruit and activate phospholipase C-γ2 (PLC-γ2), a critical effector that stimulates increases in intracellular Ca(2+) and activates various signaling pathways downstream of the BCR. Individuals with one copy of a mutant PLCG2 gene, which encodes a variant PLC-γ2 that lacks the autoinhibitory C-terminal Src homology 2 (cSH2) domain, exhibit PLC-γ2-associated antibody deficiency and immune dysregulation (PLAID). Paradoxically, although COS-7 cells expressing the variant PLC-γ2 show enhanced basal an

SUBMITTER: Wang J 

PROVIDER: S-EPMC4180509 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature