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

Tullio Florio, Hong Yao, Kendall D. Carey, Tara J. Dillon, Philip Stork

Research output: Contribution to journalArticle

119 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)24-37
Number of pages14
JournalMolecular Endocrinology
Volume13
Issue number1
DOIs
StatePublished - 1999

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Mitogen-Activated Protein Kinases
Somatostatin
Fibroblast Growth Factors
Non-Receptor Type 11 Protein Tyrosine Phosphatase
Proto-Oncogene Proteins c-raf
Phosphatidylinositol 3-Kinase
Hormones
Cyclin-Dependent Kinase Inhibitor p21
Protein Tyrosine Phosphatases
Somatostatin-Secreting Cells
Monomeric GTP-Binding Proteins
Cyclin-Dependent Kinases
CHO Cells
Protein-Serine-Threonine Kinases
Extracellular Signal-Regulated MAP Kinases
Pertussis Toxin
Growth
somatostatin receptor type 1
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Somatostatin activation of mitogen-activated protein kinase via somatostatin receptor 1 (SSTR1). / Florio, Tullio; Yao, Hong; Carey, Kendall D.; Dillon, Tara J.; Stork, Philip.

In: Molecular Endocrinology, Vol. 13, No. 1, 1999, p. 24-37.

Research output: Contribution to journalArticle

Florio, Tullio ; Yao, Hong ; Carey, Kendall D. ; Dillon, Tara J. ; Stork, Philip. / Somatostatin activation of mitogen-activated protein kinase via somatostatin receptor 1 (SSTR1). In: Molecular Endocrinology. 1999 ; Vol. 13, No. 1. pp. 24-37.
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