© 1997 American Heart Association, Inc.
Articles |
Angiotensin II Stimulates Tyrosine Phosphorylation of Phospholipase C-
–Associated Proteins
Characterization of a c-Src–Dependent 97-kD Protein in Vascular Smooth Muscle Cells
From the Department of Medicine, Division of Cardiology, University of Washington, Seattle.
Correspondence to Dr Bradford C. Berk, University of Washington, Division of Cardiology, Box 357710, Seattle, WA 98195-7710. E-mail bcberk{at}u.washington.edu
Abstract Stimulation of phospholipase C- (PLC-)
is a critical event in angiotensin II (Ang II) signal
transduction. We have previously shown that in rat aortic smooth muscle
(RASM) cells Ang II stimulates tyrosine phosphorylation
of PLC- via activation of c-Src. Because we failed to demonstrate a
direct association between c-Src and PLC-, we hypothesized that a
linker protein mediates the interaction between these molecules. To
identify PLC-–associated proteins, RASM cells were labeled with
[32P]orthophosphate and stimulated with 100 nmol/L Ang II
for 5 minutes. PLC- was immunoprecipitated, and associated proteins
were characterized by autoradiography and Western
blotting with anti-phosphotyrosine antibodies. Ang II stimulated the
phosphorylation of 47-, 60-, 84-, and 97-kD
PLC-–associated proteins. Because Ang II increased tyrosine
phosphorylation of only the 97-kD protein, we
characterized p97 further. An important role for Src in tyrosine
phosphorylation of p97 was suggested by findings that
p97 phosphorylation was inhibited by the selective
Src-family kinase inhibitor CP-118,556, diminished in mouse
aortic smooth muscle (MASM) cells from c-Src knockout mice compared
with wild-type MASM cells, and increased in v-Src–transformed NIH-3T3
cells compared with wild-type NIH-3T3 cells. These studies are the
first to define a PLC-–associated protein that may be required for
Ang II–mediated signal transduction.
Key Words: phospholipase C • angiotensin II • c-Src • smooth muscle • tyrosine kinase
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