Somatostatin Isoforms Selectively Activate the MAPK Pathway through Somatostatin Receptor Subtype One

Meeting Abstract

P2.42  Friday, Jan. 4  Somatostatin Isoforms Selectively Activate the MAPK Pathway through Somatostatin Receptor Subtype One HAGEMEISTER, A.L.*; GONG, J.; SHERIDAN, M.A.; North Dakota State Univ., Fargo

Previously we reported that rainbow trout possess two isoforms of somatostatin receptor subtype 1 (SSTR1A and SSTR1B) and that these receptors display preferential ligand binding for preprosomatostatin I (PPSS; containing SS-14 at their C-terminus)-derived peptides over PPSS II-derived peptides (containing [Tyr7, Gly10]-SS-14 at their C-terminus). In this study, we used Chinese hamster ovary cell lines (CHO-K1) stably transfected individually with trout SSTR1s to elucidate receptor-effector pathway linkages. Initially, we investigated linkages between SSTR1s and the MAPK pathway because SS-inhibited cell proliferation and growth hormone receptor (GHR) expression were accompanied by MAPK activation. PPSS I-derived peptides activated the extracellular signal-regulated kinase (ERK) subfamily of MAP kinases in a time-dependent manner in both SSTR1A- and SSTR1B-transfected cells; maximal phosphorylation of ERK occurred within 10 min. By contrast, ERK activation was not observed in cells treated with PPSS II-derived peptides. Three major components of the MAPK pathway, Raf-1, MEK1/2 and Elk1, also were activated by PPSS I-derived peptides, but not by PPSS II-derived peptides. Lastly, phosphorylation of ERK via SSTR1A and SSTR1B was pertussis toxin sensitive. These data indicate that rainbow trout SSTR1s are coupled through a G-protein-dependent mechanism to the MAPK effector pathway. In addition, selective activation of the MAPK pathway by SS isoforms may form the basis of selective regulation of cell functions by different SS peptides. (Supported by NSF IOB 0444860 to M.A.S.)

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