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Src homology domains in phospholipase C‐γ1 mediate its anti‐apoptotic action through regulating the enzymatic activity
Author(s) -
Liu Xia,
Ye Keqiang
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03064.x
Subject(s) - phospholipase , proto oncogene tyrosine protein kinase src , apoptosis , phospholipase c , biology , microbiology and biotechnology , enzyme , phospholipase d , sh2 domain , biochemistry , mutant , signal transduction , gene
Phospholipase‐γ1 (PLC‐γ1) prevents programmed cell death, for which the enzymatic activity has been implicated. However, the biological function of Src homology (SH) domains of PLC‐γ1 in promoting cell survival remains elusive. Here, we showed that deletion of the N‐SH2 domain or both N‐SH2 and C‐SH2 domains, but not the SH3 domain, abolished the anti‐apoptotic activity of PLC‐γ1. Surprisingly, removal of the whole SH domain inhibited apoptosis. The lipase‐inactive PLC‐γ1 mutant (LIM) failed to suppress apoptosis. Moreover, the phospholipase activity in SH3‐ or whole SH domain‐deleted cells was comparable to that of wild‐type cells. By contrast, the enzymatic activity was substantially ablated in SH2 domain‐deleted or LIM cells. A pharmacological inhibitor of PLC‐γ1 robustly diminished the anti‐apoptotic action in wild‐type, SH3‐ or whole SH domain‐deleted cells, whereas pretreatment of SH2 domain‐deleted or LIM cells with agents activating PKC and calcium mobilization markedly promoted cell survival. These results indicate that SH domains in PLC‐γ1 might mediate its anti‐apoptotic action by regulating the enzymatic activity.