The growing family of MAP kinases: regulation and specificity.
The family of MAP kinases consists of several subgroups of serine/threonine protein kinases. Together with their activating kinases, they function to regulate cellular responses to diverse extracellular signals, including osmotic stress, heat shock, proinflammatory cytokines, and mitogens. It is now clear that as in yeast, separate MAP kinase cascades exist in mammalian cells, responding selectively to different stimuli by phosphorylating cytoplasmic components and nuclear transcription factors. Down-regulation of MAP kinase pathways may occur through dephosphorylation by serine/threonine phosphatases, tyrosine phosphatases, or dual-specificity phosphatases and through feedback inhibitory mechanisms that involve the phosphorylation of upstream kinases. The functional integrity of each MAP kinase cascade is thought to be established and maintained by specific molecular interactions both between the kinases and with cytoplasmic anchors that nucleate complex formation. The recent demonstration that a series of pyridinyl-imidazole compounds can bind and inhibit certain MAP kinases suggests that other MAP kinase subgroups may also be susceptible to synthetic compounds. Drugs that selectively down-regulate MAP kinase cascades could prove to be valuable as therapeutic agents in the control of malignant disease.
Kortenjann
M
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Max-Planck-Institute für Immunbiologie, Spemann Laboratories, Freiburg, Germany.
Shaw
P E
PE
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D056890:Eukaryota / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007700:Kinetics; D008322:Mammals; D019950:Mitogen-Activated Protein Kinase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014157:Transcription Factors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D017027:Protein Tyrosine Phosphatases