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

Hormones and growth factors regulate cell growth via the mitogen-activated protein (MAP) kinase cascade, Here we examine the actions of the hormone so matostatin on the MAP kinase cascade through one of its two major receptor subtypes, the somatostatin receptor 1 (SSTR1) stably expressed in CHO-K1 ce lls, Somatostatin antagonizes the proliferative effects of fibroblast growt h factor in CHO-SSTR1 cells via the SSTR1 receptor, However, in these cells , somatostatin robustly activates MAP kinase (also called extracellular sig nal regulated kinase; ERK) and augments fibroblast growth factor-stimulated ERK activity, We show that the activation of ERK via SSTR1 is pertussis to xin sensitive and requires the small G protein Ras, phosphatidylinositol 3- kinase, the serine/threonine kinase Raf-1, and the protein tyrosine phospha tase 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 ac tivity mediates the growth effects of somatostatin. Our data suggest that S HP-2 stimulation by SSTR1 may mediate some of these effects through the act ivation of the MAP kinase cascade and the expression of p21(cip1/WAF1).