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Grb2 negatively regulates epidermal growth factor-induced phospholipase C-γ1 activity through the direct interaction with tyrosine-phosphorylated phospholipase C-γ1

Title
Grb2 negatively regulates epidermal growth factor-induced phospholipase C-γ1 activity through the direct interaction with tyrosine-phosphorylated phospholipase C-γ1
Authors
Jang H.C.Hong W.-P.Yun S.Hyeon S.K.Lee J.-R.Jong B.P.Yun S.B.Sung H.R.Suh P.-G.
Ewha Authors
배윤수
SCOPUS Author ID
배윤수scopus
Issue Date
2005
Journal Title
Cellular Signalling
ISSN
0898-6568JCR Link
Citation
Cellular Signalling vol. 17, no. 10, pp. 1289 - 1299
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Phospholipase C-γ1 (PLC-γ1) plays pivotal roles in cellular growth and proliferation. Upon the stimulation of growth factors and hormones, PLC-γ1 is rapidly phosphorylated at three known sites; Tyr771, Tyr783 and Tyr1254 and its enzymatic activity is up-regulated. In this study, we demonstrate for the first time that Grb2, an adaptor protein, specifically interacts with tyrosine-phosphorylated PLC-γ1 at Tyr783. The association of Grb2 with PLC-γ1 was induced by the treatment with epidermal growth factor (EGF). Replacement of Tyr783 with Phe completely blocked EGF-induced interaction of PLC-γ1 with Grb2, indicating that tyrosine phosphorylation of PLC-γ1 at Tyr783 is essential for the interaction with Grb2. Interestingly, the depletion of Grb2 from HEK-293 cells by RNA interference significantly enhanced increased EGF-induced PLC-γ1 enzymatic activity and mobilization of the intracellular Ca2+, while it did not affect EGF-induced tyrosine phosphorylation of PLC-γ1. Furthermore, overexpression of Grb2 inhibited PLC-γ1 enzymatic activity. Taken together, these results suggest Grb2, in addition to its key function in signaling through Ras, may have a negatively regulatory role on EGF-induced PLC-γ1 activation. © 2005 Elsevier Inc. All rights reserved.
DOI
10.1016/j.cellsig.2005.01.005
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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