Protein kinase isoforms

MAPK is activated by a unique dual function kinase called MEK, which is an acronym for MAPK and ERK-kinase (Crews et al, 1992 Zheng and Guan, 1993). MEK has also been named MAPK-kinase (or MAPKK) and is unusual because it phosphorylates MAPK on both a threonine and a tyrosine amino acid. MEK consists of a family of at least three protein kinase isoforms, each of which shows differential reactivity toward the different members of the MAPK family. Each MEK isoform is activated through phosphorylation mechanisms. When fully dephosphorylated, MEK is inactive. When phosphorylated by either MEK-kinase (MEKK) or the proto-oncogene raf, the phosphotransferase activity of MEK is "turned on." Although both raf and MEKK can activate MEK, differential activation of either of these kinases can lead to the activation of different downstream signal transduction pathways. Therefore, the roles of raf and MEKK in the cell are not limited to MEK and, therefore, MAPK activation. 

Gupta, S., Barrett, T., Whitmetfsh, A.J., Cavemagh, J., Sluss, H.K., Derijard, B. and Davis, R.J. 1996. Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J. 

Effect of alteration of heterocyclic nucleus of indolactam V on its isoform selectivity for protein kinase C 95F425. 

AMP-activated Protein Kinase. Table 1 Information about subunit isoforms of AMP-activated protein kinase. Data refer to the full-length forms of the human isoforms. The y2 and y3 isoforms also exist as splice variants that are N-terminal truncations, with lower molecular mass and number of amino acids (38 kDa and 328 amino acids for the short form of y2, 52 kDa and 464 amino acids for the short form of y3). Other splice variants may also exist... 

Deehan, M., Harnett, M. and Harnett, W. (1997) A filarial nematode secreted product differentially modulates expression and activation of protein kinase C isoforms in B lymphocytes. Journal of Immunology 159, 6105-6111. 

I. The phosphatidylinositide 3-kinase (PI 3-kinase) pathway, in particular, effects mediated through its effector protein kinase B (PKB, also termed Akt three isoforms) ... 

MAP kinase signaling modules typically comprise a cassette of three protein kinases (Fig. 7.2A). For example, ERK (two isoforms in mammalian cells, ERK1/2) is phosphorylated (at Thr and Tyr residues in the activation loop of its catalytic domain by an upstream MAP kinase kinase (in this case, MEK) which is, in turn, phosphorylated and activated by a MAP kinase kinase kinase, in this instance, a member of the Raf group) (Fig. 7.2A). 

Sutherland, C., and Cohen, P. (1994). The alpha-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is inactivated by p70 S6 kinase or MAP kinase-activated protein kinase-1 in vitro. FEBS Lett. 338, 37—42. 

Neurexins a protein kinase. A component of active zones that interact with RIM, syntaxin and other proteins. Cell surface proteins with more than 1,000 isoforms generated by alternative splicing from three genes. Neurexins include one of the receptors for aratrotoxin and may function in cell-cell recognition between neurons. 

Protein kinase C (PKC) comprises the other major class of Ca2+-dependent protein kinases and is activated by Ca2+ in conjunction with DAG and phosphatidylserine (discussed in Ch. 20). Multiple forms of PKC have been cloned, and the brain is known to contain at least seven species of the enzyme. The variant forms of PKC exhibit different cellular distributions in the brain and different regulatory properties. For example, they differ in the relative ability of Ca2+ and DAG to activate them some require both Ca2+ and DAG, whereas others can be activated by DAG alone, apparently without an increase in cellular Ca2+ concentrations. However, these enzymes show similar substrate specificities and, as a result, are often considered isoforms. 

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