La estimulación de MAPK por el receptor de la ghrelina GHS-R1a requiere la endocitosis del receptor. Interdependencia entre beta-arrestina y la proteína Gi.

LODEIRO-POSE M; ISCHENKO O; MARTINI AC; PÉREZ ROMERO S; LAGE M; CASANUEVA FF; CAMIÑA J

Sevilla, España

Congreso; 48 Congreso de la Sociedad Española deEndocrinología y Nutrición; 2006

Sociedad Española deEndocrinología y Nutrición

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 b-arrestins 1 and 2, and requires entry of the receptor into a multiprotein complex with the b-arrestins, Src, Raf-1, and ERK 1/2. A second pathway is Gq/11-dependent and involves a Ca2+-dependent PKC (PKCa/b) and Src. A third pathway is Gi-dependent and involves phosphoinositide 3-kinase (PI3K), PKCe, and Src.Our current study reveals that Gi/0 and Gq/11-proteins are crucially envolved in the b-arrestin-mediated ERK 1/2 activation. These results tus support the view that b-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.