Somatostatin activation of mitogen-activated protein kinase via somatostatin receptor 1 (SSTR1)

Mol Endocrinol. 1999 Jan;13(1):24-37. doi: 10.1210/mend.13.1.0224.

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