Stimulation by ghrelin of p42/p44 mitogen-activated proten kinase through the GHS-R1a receptor: role of G-proteins and beta-arrestins.

CAMIÑA J; LODEIRO M; ISCHENKO O; MARTINI AC; CASANUEVA FF

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2007 vol. 213 p. 187 - 200

0021-9541

Results presented in this study indicate that in human embryonic kidney 293 cells (HEK 293), the ghrelin receptor growth hormona secretagogue receptor type 1a (GHS-R1a) activated the extracellular signal-related kinases 1 and 2 (ERK 1/2) via three pathways. One pathway is mediated by the beta-arrestins 1 and 2, and requires entry of the receptor into a multiprotein complex with the beta-arrestins, Src, Raf-1 and ERK 1/2. A second pathway is Gq/11-dependent and involves a Ca2+-dependent PKC (PKCalfa/beta)and Src. A third pathway is Gi-dependent and involves phosphoinositide 3-kinase (PI3K), PKCepsilon and Src.Our current study reveals that Gi/0- and Gq/11-proteins are crucially envolved in the beta-arrestin-mediated ERK 1/2 activation. These results tus support the view that beta-arrestins act as both scaffolding proteins and signal transducers in ERK 1/2 activation, as reproted for other receptors. The different pathway of ERK 1/2 activation suggest that binding to GHS-R1a activates ERK 1/2 pools at different locations within the cell, and tus probable with different physiological consequences.