Somatostatin Activation of Mitogen-Activated Protein Kinase via Somatostatin Receptor 1 (SSTR1)

• DOI: 10.1210/mend.13.1.0224
• Publication Date: 2014-01-08T17:29:59Z
• Authors: Tullio Florio; Hong Yao; Kendall D. Carey; Tara J. Dillon; Philip J. S. Stork
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; Protein Tyrosine Phosphatase, Non-Receptor Type 1; 0301 basic medicine; 0303 health sciences; Mitogen-Activated Protein Kinase 3; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Intracellular Signaling Peptides and Proteins; Protein Tyrosine Phosphatase, Non-Receptor Type 11; CHO Cells; Protein-Tyrosine Kinases; Enzyme Activation; Proto-Oncogene Proteins c-raf; 03 medical and health sciences; Pertussis Toxin; GTP-Binding Proteins; Cricetinae; Cyclins; Calcium-Calmodulin-Dependent Protein Kinases; Animals; Fibroblast Growth Factor 2; Mitogen-Activated Protein Kinases; Protein Tyrosine Phosphatases; Cell Division

AbstractHormones 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 p21cip1/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 p21cip1/WAF1.