Rainbow trout somatostatin receptor subtypes SSTR1A, SSTR1B, and SSTR2 differentially activate the extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling pathways in transfected cells.
Previously, we reported that extracellular signal-regulated kinase (ERK) and protein kinase B (Akt), a downstream target of phosphatidylinositol 3-kinase (PI3K), mediated somatostatin (SS) inhibition of GH receptor, IGF1, and IGF1 receptor expression. In this study, we used Chinese hamster ovary-K1 cells that stably transfected individually with trout SS receptors (SSTR1A, SSTR1B, and SSTR2) to elucidate receptor-effector pathway linkages. SS induced ERK and Akt activation in a time- and concentration-related manner in all SSTR-expressing cells; however, the PI3K/Akt pathway was activated to a greater extent through SSTR1A than through either SSTR1B or SSTR2, whereas the ERK pathway was activated to a greater extent though SSTR2 than through either SSTR1A or SSTR1B. Although the ERK pathway inhibitor U0126 had no effect on Akt activation, the PI3K inhibitor LY294002 reduced ERK activation to near control levels in all SSTR-expressing cell lines, suggesting some cross talk between the pathways, possibly at the level of c-Raf, the phosphorylation of which also was induced by SS via each SSTR. Pertussis toxin (PTX) completely abolished SS-induced activation of ERK and Akt in SSTR1A-, SSTR1B-, and SSTR2-expressing cells, suggesting that these receptors link to the ERK and PI3K/Akt pathways via PTX-sensitive G-proteins. SS-induced activation of Elk1, Stat3, and C/EBPβ also was mediated by each of the trout SSTRs. These findings establish important receptor-effector pathway linkages for fish SSTRs and provide insight into the molecular mechanisms by which SSs may elicit diverse physiological effects in target cells.
Hagemeister
Alison L
AL
Department of Biological Sciences, North Dakota State University, Department 2715, PO Box 6050, Fargo, North Dakota 58108-6050, USA.
Kittilson
Jeffrey D
JD
Bergan
Heather E
HE
Sheridan
Mark A
MA
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; C093733:somatostatin receptor 2; D037342:Pertussis Toxin; D058539:Phosphatidylinositol 3-Kinase; D048049:Extracellular Signal-Regulated MAP Kinases