Premium
Regulation of EGF‐Induced Phospholipase C‐γ1 Translocation and Activation by its SH2 and PH Domains
Author(s) -
Wang Yi,
Wang Zhixiang
Publication year - 2003
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1034/j.1600-0854.2003.00121.x
Subject(s) - phospholipase , phospholipase c , biology , microbiology and biotechnology , epidermal growth factor , phosphoinositide phospholipase c , endosome , cytosol , chromosomal translocation , phospholipase d , c2 domain , phospholipase a1 , signal transduction , biochemistry , enzyme , receptor , membrane , intracellular , gene
Translocation of phospholipase C‐γ1 is essential for its function in response to growth factors. However, in spite of recent progress, the phospholipase C‐γ1 translocation pattern and the molecular mechanism of the translocation are far from fully understood. Contradictory results were reported as to which domain, PH or SH2, controls the epidermal growth factor‐induced translocation of phospholipase C‐γ1. In this communication, we studied epidermal growth factor‐induced translocation of phospholipase C‐γ1 by using comprehensive approaches including biochemistry, indirect fluorescence and live fluorescence imaging. We provided original evidence demonstrating that: (i) endogenous phospholipase C‐γ1, similar to YFP‐tagged phospholipase C‐γ1, translocated to endosomes following its initial translocation from cytosol to the plasma membrane in response to epidermal growth factor; (ii) phospholipase C‐γ1 remained phosphorylated in endosomes, but phospholipase C‐γ1 activity is not required for its translocation, which suggests a signaling role for phospholipase C‐γ1 in endosomes; (iii) the PH domain was not required for the initial translocation of phospholipase C‐γ1 from cytosol to the plasma membrane, but it stabilizes phospholipase C‐γ1 in the membrane at a later time; (iv) the function of the phospholipase C‐γ1 PH domain in stabilizing phospholipase C‐γ1 membrane association is very important in maintaining the activity of phospholipase C‐γ1; and (v) the role of the PH domain in phospholipase C‐γ1 membrane association and activation is dependent on PI3K activity. We conclude that the phospholipase C‐γ1 SH2 and PH domains coordinate to determine epidermal growth factor‐induced translocation and activation of phospholipase C‐γ1.