Regulation of MAPKs by growth factors and receptor tyrosine kinases.
Multiple growth- and differentiation-inducing polypeptide factors bind to and activate transmembrane receptors tyrosine kinases (RTKs), to instigate a plethora of biochemical cascades culminating in regulation of cell fate. We concentrate on the four linear mitogen-activated protein kinase (MAPK) cascades, and highlight organizational and functional features relevant to their action downstream to RTKs. Two cellular outcomes of growth factor action, namely proliferation and migration, are critically regulated by MAPKs and we detail the underlying molecular mechanisms. Hyperactivation of MAPKs, primarily the Erk pathway, is a landmark of cancer. We describe the many links of MAPKs to tumor biology and review studies that identified machineries permitting prolongation of MAPK signaling. Models attributing signal integration to both phosphorylation of MAPK substrates and to MAPK-regulated gene expression may shed light on the remarkably diversified functions of MAPKs acting downstream to activated RTKs.
Katz
Menachem
M
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Amit
Ido
I
Yarden
Yosef
Y
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D004705:Endocytosis; D005246:Feedback; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D009857:Oncogenes; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism; D020239:Receptor Cross-Talk; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
D006133:Growth Substances; D016601:RNA-Binding Proteins; D020794:Receptor Protein-Tyrosine Kinases