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- Title
Involvement of protein tyrosine phosphatase SHP-1 in the inhibition of membrane-bound guanylate cyclase GC-A activity stimulated by atrial natriuretic factor.
- Authors
Chung-Ho Chang; Geen-Dong Chang; Su-Rong Yang; Chen-Yu Chen; Wan-Yu Chung
- Abstract
We examined whether SHP-1 can regulate the activation of membrane-bound guanylate cyclase GC-A by atrial natriuretic factor (ANF). Coimmunoprecipitation experiments indicated that SHP-I associated with GC-A in an ANF-dependent manner. Transfection of SHP-1 into CHO and MCF-7 cells inhibited ANF-stimulated GC-A activity. GC-A contains two SHP-1 substrate consensus sequences (amino acids 816-821 and 1014-1020) in its catalytic domain (GC-c). Transfection studies showed that SHP-1 inhibited the activity of GC-c, indicating that SHP-1 interacts with the catalytic domain. Interestingly, substitution of Phe at Tyr 818 or Tyr 1017 on GC-c led to the loss of enzyme activity. Examination of the tyrosine phosphorylation state of GC-A reveals that GC-A is not dephosphorylated by SHP-1. Transfection of v-Src enhanced ANF-stimulated GC-A activity in MCF-7 cells, whereas inhibition of Src activity decreased it. Co-immunoprecipitation experiments indicate that transfection of SHP-1 disrupts the association of Src with GC-A. These results indicate that SHP-1 is a GC-A associated protein, and that SHP-1 inhibits the activity of GC-A at least partly by disrupting the association of Src with GC-A. This work was supported by grants from the National Institute of Health and the National Science Council.
- Subjects
UNITED States; GUANYLATE cyclase; ATRIAL natriuretic peptides; AMINO acids; ENZYMES; LYASES; NATIONAL Science &; Technology Council (U.S.); NATIONAL Institutes of Health (U.S.)
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA797
- ISSN
0892-6638
- Publication type
Article