Abstract
Hormones and growth factors regulate cell growth via the mitogen-activated protein (MAP) kinase cascade. Here we examine the actions of the hormone somatostatin on the MAP kinase cascade through one of its two major receptor subtypes, the somatostatin receptor 1 (SSTR1) stably expressed in CHO-K1 cells. Somatostatin antagonizes the proliferative effects of fibroblast growth factor in CHO-SSTR1 cells via the SSTR1 receptor. However, in these cells, somatostatin robustly activates MAP kinase (also called extracellular signal regulated kinase; ERK) and augments fibroblast growth factor-stimulated ERK activity. We show that the activation of ERK via SSTR1 is pertussis toxin sensitive and requires the small G protein Ras, phosphatidylinositol 3-kinase, the serine/threonine kinase Raf-1, and the protein tyrosine phosphatase SHP-2. The activation of ERK by SSTR1 increased the expression of the cyclin-dependent protein kinase inhibitor p21(cip1/WAF1). Previous studies have suggested that somatostatin-stimulated protein tyrosine phosphatase activity mediates the growth effects of somatostatin. Our data suggest that SHP-2 stimulation by SSTR1 may mediate some of these effects through the activation of the MAP kinase cascade and the expression of p21(cip1/WAF1).
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
CHO Cells / drug effects
-
CHO Cells / metabolism
-
Calcium-Calmodulin-Dependent Protein Kinases / drug effects
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
-
Cell Division
-
Cricetinae
-
Cyclin-Dependent Kinase Inhibitor p21
-
Cyclins / drug effects
-
Cyclins / metabolism
-
Enzyme Activation / drug effects
-
Fibroblast Growth Factor 2 / pharmacology
-
GTP-Binding Proteins / drug effects
-
GTP-Binding Proteins / metabolism
-
Intracellular Signaling Peptides and Proteins
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases*
-
Pertussis Toxin
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11
-
Protein Tyrosine Phosphatase, Non-Receptor Type 6
-
Protein Tyrosine Phosphatases / metabolism
-
Protein-Tyrosine Kinases / metabolism
-
Proto-Oncogene Proteins c-raf / genetics
-
Proto-Oncogene Proteins c-raf / metabolism
-
Receptors, Somatostatin / genetics
-
Receptors, Somatostatin / metabolism*
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
SH2 Domain-Containing Protein Tyrosine Phosphatases
-
Somatostatin / metabolism*
-
Somatostatin / pharmacology
-
Virulence Factors, Bordetella / pharmacology
-
ras Proteins / genetics
-
ras Proteins / metabolism
-
src Homology Domains
Substances
-
Cyclin-Dependent Kinase Inhibitor p21
-
Cyclins
-
Intracellular Signaling Peptides and Proteins
-
Receptors, Somatostatin
-
Recombinant Proteins
-
Virulence Factors, Bordetella
-
somatostatin receptor type 1
-
Fibroblast Growth Factor 2
-
Somatostatin
-
Pertussis Toxin
-
Protein-Tyrosine Kinases
-
Proto-Oncogene Proteins c-raf
-
Calcium-Calmodulin-Dependent Protein Kinases
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11
-
Protein Tyrosine Phosphatase, Non-Receptor Type 6
-
Protein Tyrosine Phosphatases
-
SH2 Domain-Containing Protein Tyrosine Phosphatases
-
GTP-Binding Proteins
-
ras Proteins