Dual specificity

MAPK cascades are composed of three cytoplasmic kinases, the MAPKKK, MAPKK, and MAPK, that are regulated by phosphorylation (Fig. 1) [1, 2]. The MAPKKK, also called MEKK for MEK kinase, is a serine/threonine kinase. Selective activation of MAPKKKs by upstream cellular stimuli results in the phosphorylation of MAPKK, also called MEK for MAP/ERK kinase by the MAPKKK. MAPKKK members are structurally diverse and are differentially regulated by specific upstream stimuli. The MAPKK is phosphorylated by the MAPKKK on two specific serine/ threonine residues in its activation loop. The MAPKK family members are dual specificity kinases capable of phosphorylating critical threonine and tyrosine residues in the activation loop of the MAPKs. MAPKKs have the fewest members in the MAPK signaling module. MAPKs are a family of serine/threonine kinases that upon activation by their respective MAPKKs, are capable of phosphorylating cytoplasmic substrates as well as... 

The classical PTPs can be subdivided into receptorlike PTPs and nonreceptor, cytosolic PTPs. The second category of PTPs are broadly defined as dual specificity phosphatases (DSPs), which dephosphorylate pSer/ pThr as well as pTyr. MAP kinase phosphatases (MKPs) ( MAP kinase cascades) and PTEN are examples of DSP family members. Remarkably, PTEN also has lipid phosphatase activity that is specific for phosphatidylinositol-3,4,5-trisphosphate generated in response to the actions of PI3K. Finally, the class of low molecular mass (LM-) PTPs and that of CDC25 PTPs accomplish the cells repertoire of PTPs (Fig. 3). 

Receptor like Cytosolic Dual specific Low molecular CDC25... 

Letwin, K., Mizzen, L., Motro, B., Ben-David, Y., Berstein, A., and Pawson, T. (1992). A mammalian dual specificity protein kinase, Nekl, is related to NIMA cell cycle regulator and highly expressed in meiotic germ cells. EMBO J. 11 3521-3531. 

Nakielny, S., Campbell, D. G., and Cohen, P. (1992b). MAP kinase kinase from rabbit skeletal muscle a novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone-dependent signal transduction. FEBS Lett. 308 183-189. 

Van Paridon, P. A., Gadella, J. T. W. J., Somerharju, P. J. and Wirtz, K. W. A. (1987). On the relationship between the dual specificity of the bovine brain phosphatidylinositol transfer protein and membrane phosphatidylinositol levels. Biochim. Biophys. Acta 903, 68-77. 

Keyse, S. M. An emerging family of dual specificity MAP kinase phosphatases. Biochim. Biophys. Acta 1265 152-160, 1995. 

DSPc Dual specificity phosphatase, catalytic domain E(MFP)B 5(5) 10(10) 1VHR... 

Gong, L., Kamitani, T., Millas, S., and Yeh, E. T. Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins, J Biol Chem, 2000, 275, 14212-6. 

AspRSs of dual specificity involved in tRNA asparaginylation have first been characterized in archaea and in the Deinococcales (T. thermophilus and D. radiodurans). Interestingly, these eubacteria contain two AspRSs the... 

Table 1 Some known protein tyrosine, serine/threonine and dual specificity kinases...

Non-receptor serine/threonine kinases and dual specificity kinases cAMP-dependent protein kinase (PKA) Phosphoinositol-3-kinase (PI-3K) Cyclin-dependent kinase (CDK) Mitogen-activated protein kinase (MAPK) MAPKK (ERK)... 

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