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

Hyun Choi Jang, Won Pyo Hong, Sanguk Yun, Hyeon Soo Kim, Jong Ryul Lee, Bae Park Jong, Soo Bae Yun, Ho Ryu Sung, Pann Ghill Suh

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1289-1299
Number of pages11
JournalCellular Signalling
Volume17
Issue number10
DOIs
Publication statusPublished - 2005 Oct 1
Externally publishedYes

Fingerprint

Type C Phospholipases
Epidermal Growth Factor
Tyrosine
Phosphorylation
HEK293 Cells
RNA Interference
Growth Hormone
Intercellular Signaling Peptides and Proteins
Cell Proliferation

Keywords

  • Epidermal growth factor
  • Grb2
  • Interaction
  • Phospholipase C-γ1
  • Suppression
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Grb2 negatively regulates epidermal growth factor-induced phospholipase C-γ1 activity through the direct interaction with tyrosine-phosphorylated phospholipase C-γ1. / Jang, Hyun Choi; Hong, Won Pyo; Yun, Sanguk; Kim, Hyeon Soo; Lee, Jong Ryul; Jong, Bae Park; Yun, Soo Bae; Sung, Ho Ryu; Suh, Pann Ghill.

In: Cellular Signalling, Vol. 17, No. 10, 01.10.2005, p. 1289-1299.

Research output: Contribution to journalArticle

Jang, Hyun Choi ; Hong, Won Pyo ; Yun, Sanguk ; Kim, Hyeon Soo ; Lee, Jong Ryul ; Jong, Bae Park ; Yun, Soo Bae ; Sung, Ho Ryu ; Suh, Pann Ghill. / Grb2 negatively regulates epidermal growth factor-induced phospholipase C-γ1 activity through the direct interaction with tyrosine-phosphorylated phospholipase C-γ1. In: Cellular Signalling. 2005 ; Vol. 17, No. 10. pp. 1289-1299.
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