Regulation of the ERK subgroup of MAP kinase cascades through G protein-coupled receptors.
The extracellularly-responsive kinase (ERK) subfamily of mitogen-activated protein kinases (MAPKs) has been implicated in the regulation of cell growth and differentiation. Activation of ERKs involves a two-step protein kinase cascade lying upstream from ERK, in which the Raf family are the MAPK kinase kinases and the MEK1/MEK2 isoforms are the MAPK kinases. The linear sequence of Raf --> MEK --> ERK constitutes the ERK cascade. Although the ERK cascade is activated through growth factor-regulated receptor protein tyrosine kinases, they are also modulated through G protein-coupled receptors (GPCRs). All four G protein subfamilies (Gq/11 Gi/o, Gs and G12/13) influence the activation state of ERKs. In this review, we describe the ERK cascade and characteristics 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.
Sugden
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PH
National Heart and Lung Institute (Cardiac Medicine), Imperial College School of Medicine, London, United Kingdom.
Clerk
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D004789:Enzyme Activation; D048369:MAP Kinase Kinase 1; D008565:Membrane Proteins / Q000737:chemistry; D020929:Mitogen-Activated Protein Kinase Kinases; D009097:Multienzyme Complexes / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
C029152:G-substrate; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases