Diversity of G protein-coupled receptor signaling pathways to ERK/MAP kinase

Abstract

One of the most intriguing examples of cross talk between signaling systems is the interrelationship between G protein-coupled receptor and growth factor receptor pathways leading to activation of the ERK/MAP kinase phosphorylation cascade. This review focuses on the mechanism of this cross talk, denoting primarily signaling components known to occur in the G protein-coupled receptor branch of the MAP kinase pathways in neural cells. Recent evidence is presented on the existence of a plethora of pathways, due to the multiplicity of G protein-coupled receptors, their differential interaction with heterotrimeric G protein isoforms, various effectors and second messengers. In light of this rich diversity, the review will discuss different points of convergence of G protein-coupled receptor and growth factor receptor pathways that may feature a requirement for growth factor receptor transactivation, receptor internalization and scaffolds to assemble receptor, adaptor and anchoring proteins into multiprotein complexes.

Fig. 1

Diversity of GPCR signaling pathways to ERK/MAP kinase. The various signaling components are shaped according to their function as follows: G proteins as vertical ellipses, nonreceptor Tyr kinases as horizontal ellipses, Ser-Thr kinases as larger octagons, lipids as small octagons, adaptor proteins as rounded rectangles, Ca²⁺ as circles. B-Arr = β-Arrestin; IP₃ = inositol triphosphate; MMP = matrix metalloproteases; PtdIns = phosphatidylinositide.