Src tyrosine kinase is a novel direct effector of G proteins

Yong Chao Ma, Jianyun Huang, Shariq Ali, William Lowry, Xin Yun Huang

Research output: Contribution to journalArticlepeer-review

368 Scopus citations

Abstract

Heterotrimeric G proteins transduce signals from cell surface receptors to modulate the activity of cellular effectors. Src, the product of the first characterized proto-oncogene and the first identified protein tyrosine kinase, plays a critical role in the signal transduction of G protein-coupled receptors. However, the mechanism of biochemical regulation of Src by G proteins is not known. Here we demonstrate that Gαs and Gαi, but neither Gαq, Gα12 nor Gβγ, directly stimulate the kinase activity of downregulated c-Src. Gαs and Gαi similarly modulate Hck, another member of Src-family tyrosine kinases. Gαs and Gαi bind to the catalytic domain and change the conformation of Src, leading to increased accessibility of the active site to substrates. These data demonstrate that the Src family tyrosine kinases are direct effectors of G proteins.

Original languageEnglish (US)
Pages (from-to)635-646
Number of pages12
JournalCell
Volume102
Issue number5
DOIs
StatePublished - Sep 1 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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