Camiña Jesus P, Lodeiro Maria, Ischenko Olga, Martini Ana C, Casanueva Felipe F
Laboratory of Molecular Endocrinology, Research Area, Complejo Hospitalario Universitario de Santiago (CHUS) and Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
J Cell Physiol. 2007 Oct;213(1):187-200. doi: 10.1002/jcp.21109.
Results presented in this study indicate that in human embryonic kidney 293 cells (HEK 293), the ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a) activates 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 G(q/11)-dependent and involves a Ca(2+)-dependent PKC (PKCalpha/beta) and Src. A third pathway is G(i)-dependent and involves phosphoinositide 3-kinase (PI3K), PKCepsilon, and Src. Our current study reveals that G(i/o)- and G(q/11)-proteins are crucially involved in the beta-arrestin-mediated ERK 1/2 activation. These results thus support the view that the beta-arrestins act as both scaffolding proteins and signal transducers in ERK 1/2 activation, as reported for other receptors. The different pathways of ERK 1/2 activation suggest that binding to GHS-R1a activates ERK 1/2 pools at different locations within the cell, and thus probably with different physiological consequences.
本研究给出的结果表明，在人胚肾293细胞（HEK 293）中，胃饥饿素受体1a型生长激素促分泌素受体（GHS-R1a）通过三条途径激活细胞外信号调节激酶1和2（ERK 1/2）。一条途径由β-抑制蛋白1和2介导，需要受体进入与β-抑制蛋白、Src、Raf-1和ERK 1/2形成的多蛋白复合物。第二条途径依赖G(q/11)，涉及钙依赖性蛋白激酶C（PKCα/β）和Src。第三条途径依赖G(i)，涉及磷脂酰肌醇3激酶（PI3K）、PKCε和Src。我们目前的研究表明，G(i/o)蛋白和G(q/11)蛋白在β-抑制蛋白介导的ERK 1/2激活中起关键作用。因此，这些结果支持了如下观点：如其他受体的报道一样，β-抑制蛋白在ERK 1/2激活中既作为支架蛋白又作为信号转导分子。ERK 1/2激活的不同途径表明，与GHS-R1a的结合激活了细胞内不同位置的ERK 1/2库，因此可能具有不同的生理后果。
