ERK, Akt, and STAT5 are Differentially Activated by the Two Growth Hormone Receptor Subtypes of a Teleost Fish (Oncorhynchus Mykiss)

Previously, we found that the teleost fish, rainbow trout, possesses two growth hormone receptor (GHR) subtypes that display distinct ligand-binding and agonist-induced regulation features. In this study, we used Chinese hamster ovary-K1 cells stably transfected individually with the two trout GHR subtypes, GHR1 and GHR2, to elucidate receptor–effector pathway linkages. Growth hormone (GH) stimulated rapid (5–10 min) phosphorylation of ERK, Akt, JAk2, and STAT5 in both GHR1- and GHR2-expressing cells; however; STAT5 was activated to a greater extent through GHR1 than through GHR2, whereas ERK and Akt were activated to a greater through GHR2 than through GHR1. Although blockade of the ERK pathway had no effect on the activation of Akt, inhibition of PI3K–Akt partially prevented activation of ERK, suggesting cross-talk between the ERK and PI3K–Akt pathways. JAK2 inhibition completely blocked activation of ERK, Akt, and STAT5, suggesting that all of these pathways link to GHR1 and GHR2 via JAK2. These findings establish important receptor–effector pathway linkages and suggest that the GHR subtypes of teleost fish may be functionally distinct.