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Thrombin activates phosphoinositide 3-kinase (PI 3-kinase) in platelets via a mechanism involving G-proteins, possibly of both the heterotrimeric and the low molecular weight families. We have investigated the regulation of PI 3-kinase present in platelet cytosol, and we show that this activity can be stimulated by a mixed preparation of G-protein beta gamma-subunits. This stimulation is reversed by preincubation of the beta gamma-subunits with GDP-liganded alpha-subunits. The beta gamma-stimulated activity is inhibited by wortmannin, a recently identified inhibitor of PI 3-kinase in other systems. In addition, the activity associates with PDGF receptor phosphotyrosyl peptide and monoclonal antibody designed to interact with the p85 subunit of PI 3-kinase. We suggest that this beta gamma-sensitive activity is related to previously identified forms of PI 3-kinase.
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
January 1995,
Methods in enzymology,
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
April 1994,
Cell,
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
September 1995,
Molecular pharmacology,
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
March 1995,
The Journal of biological chemistry,
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
February 2000,
Science (New York, N.Y.),
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
March 2002,
FEBS letters,
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
June 1997,
The Biochemical journal,
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
May 1997,
The Journal of biological chemistry,
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
January 2003,
The Journal of cell biology,
P A Thomason, and
S R James, and
P J Casey, and
C P Downes
August 1995,
Science (New York, N.Y.),
