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 language | English (US) |
|---|---|
| Pages (from-to) | 635-646 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 102 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 1 2000 |
Funding
We thank W. Xu for purified c-Src, recombinant baculovirus encoding c-Src, and help on purification of c-Src; T. Schindler and J. Kuriyan for purified Hck and recombinant baculoviruses encoding Hck; P. Cole for purified Csk and bacterial stock harboring Csk plasmid; and T. Kozasa, A. Gilman, and C. Berlot for the Gαs and Gαi plasmid DNAs. We are grateful to Drs. M. Chao, M. Gershengorn, L. Levin, and T. Maack for discussion and reading the manuscript. Research in our lab is supported by grants from the NIH (AG14563 and GM56904), the American Cancer Society, and the Dorothy Rodbell Cohen Foundation for Sarcoma Research. X.-Y. H. is an Established Investigator of the American Heart Association and a Career Scientist of the Irma T. Hirschl Trust.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology