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

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

Research output: Contribution to journalArticle

120 Scopus citations

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 - Jan 1 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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