REGULATION OF THE ERK SUBGROUP OF MAP KINASE CASCADES THROUGH G-PROTEIN-COUPLED RECEPTORS

The extracellularly-responsive kinase (ERK) subfamily of mitogen-activ ated protein kinases (MAPKs) has been implicated in the regulation of cell growth and differentiation. Activation of ERKs involves a two-ste p protein kinase cascade lying upstream from ERK, in which the Raf fam ily are the MAPK kinase kinases and the MEK1/MEK2 isoforms are the MAP K kinases. The linear sequence of Raf --> MEK --> ERK constitutes the ERK cascade. Although the ERK cascade is activated through growth fact or-regulated receptor protein tyrosine kinases, they are also modulate d through G protein-coupled receptors (GPCRs). All four CT protein sub families (G(q/11), G(i/o) G(s) and G(12/13)) influence the activation state of ERKs. In this review, we describe the ERK cascade and charact eristics of its activation through GPCRs. We also discuss the identity of the intervening steps that may couple agonist binding at GPCRs to activation of the ERK cascade. (C) 1997 Elsevier Science Inc.