Passing the Baton: New gene might get the handoff from growth hormone

Abstract

In a relay race, the lead and anchor legs get the glory. But the middle runners are crucial for propelling the team from start to finish. A newly identified gene might run the second stretch in a cellular signaling race by taking the stick from growth hormone (GH). Mounting evidence suggests that a cellular signaling pathway triggered by GH in mammals can influence life-span in fruit flies, worms, and possibly mice: Some animals that carry mutations in the insulin/insulin-like growth factor 1 (IGF-1) pathway live significantly longer than normal. Although the binding of GH to cells eventually stimulates IGF-1, the genes that respond directly to GH remain mysterious. New work points to a potential target. Lu and colleagues engineered rat heart muscle cells to produce the GH receptor and then added growth hormone to half of the cells. Using microarrays, the team analyzed messenger RNA (mRNA) from treated and untreated samples to identify genes that ramped up or down in response to the hormone. The amount of one gene's transcript increased fourfold. When the researchers injected mice with GH, mRNA production from the mouse version of this gene--which they called Grtp1 , for GH-regulated TBC protein-1--increased in testes (where the gene is most highly expressed, even at base levels). The amount of Grtp1 mRNA decreased in kidney and liver. This result suggests that GH controls expression of Grtp1 in intact animals as well as in isolated cells. No one knows the function of Grtp1 , but its predicted amino acid sequence contains a so-called TBC motif. This domain lies in activators of GTPases, proteins that use the small signaling molecule GTP to turn on and off cellular signaling pathways. Together, these proteins flip molecular switches to control processes such as cell division. The team found genes that resemble Grtp1 in humans and fruit flies in addition to rats and mice. This observation hints that Grtp1 's function--whatever it might be--is well conserved. It also gives researchers multiple systems in which to test whether Grtp1 runs a leg in the aging race. C. Lu, J. Kasik, D. A. Stephan, S. Yang, M. A. Sperling, R. K. Menon, Grtp1 , a novel gene regulated by growth hormone. Endocrinology 142 , 4568-4571 (2001). [Abstract] [Full Text] --Suggested by James M. Harper