Mitogen-activated protein kinase family

Poteet-Smith, C. E., Smith, J. A., Lannigan, D. A., Freed, T. A., and Sturgill, T. W. (1999). Generation of constitutively active p90 ribosomal S6 kinase in vivo. Implications for the mitogen-activated protein kinase-activated protein kinase family. J. Biol. Chem. 274, 22135-22138. 

Mitogen-activated protein kinase phosphatases are dual-function protein phosphatases. Just as the MAPK kinases (e.g. MEKs) are unique as dual-functioning kinases in that they phosphorylate MAPKs on threonine and tyrosine residues, there are unique dual-function ing protein phosphatases that reverse the phosphorylation and activation of MAPKs [43], Such MAPK phosphatases (MKPs) were first identified as a product of vaccinia virus (VH1) and later found in all eukaryotic cells. There are now numerous members of this VH1 family of dual-functioning protein phosphatases. 

Another important family of kinases for drug discovery is the mitogen-activated protein kinases (MAPKs). These are proline-directed serine/threonine kinases that activate their substrates by dual-phosphorylation. MAPK enzymes are activated by a variety of signals including growth factors and cytokines, discussed in chapter 6. The MAPK family plays a critical role in cell cycle progression. Small molecule inhibitors of MAPK may have utility in the treatment of cancer. 

Tortarolo M., Veglianese P., Calvaresi N., Botturi A., Rossi C., Giorgini A., Migheli A., and Bendotti C. (2003). Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression. Mol. Cell. Neurosci. 23 180-192. 

The 5-HT1A receptor is a member of the 5-HT] family of serotonin receptors best known for their capacity to inhibit adenylyl cyclase activity via pertussis toxin-sensitive G proteins. These receptors also couple to K+ channels, Ca2+ channels, PLC, intracellular calcium, mitogen-activated protein kinase cascade, and Na+/K+-ATPase (73,74). This receptor is an important target for the management of anxiety, depression, and schizophrenia (75-78). 

Vitale G, Bernardi L, Napolitani G et al (2000) Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem J 352 739-745... 

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