Kinases 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... 

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)... 

Fig. 10.2. Components and activation of the ERK pathway. Ordering and specificity of protein kinases in the ERK pathway. ExtraceUular signals are registered via receptor tyrosine kinases and passed on to the Ras protein. Ras GTP activates protein kinases belonging to the group of MAPKK kinases (Raf kinases and MEEKs). The MAPKK kinases phosphorylate the downstream group of protein kinases, the MAPKKs at two Ser residues. The MAPKKs phosphorylate the MAPKs (ERKl and ERK2) at a Tyr and a Thr residue, and thus are classified as dual specificity kinases. MAPK mitogenic activated protein kinase ERK extracellularly regulated kinase MEK MAP/ERK kinase MAPKK MAPK kinase MAPKKK MAPKK kinase MEKK MEK kinase.

Dhanasekaran, N. and Reddy, E.P Signaling by dual specificity kinases (1998) Oncogene 17, 1447-1456... 

Dual specificity kinases Mitogen-uclivetcd protein kinase... 

Poch, O. Schwob, E. de Fraipont, E Camasses, A. Bordonne, R. Martin, R.P. RPKl, an essential yeast protein kinase involved in the regulation of the onset of mitosis, shows homology to mammalian dual-specificity kinases. Mol. Gen. Genet, 243, 641-653 (1994)... 

Nuckolls, G.H. Osherov, N. Loomis, W.F. Spudich, J.A. The Dictyoste-lium dual-specificity kinase splA is essential for spore differentiation. Development, 122, 3295-3305 (1996)... 

MAPKK is a serine/threonine kinase that will be activated by MAPKKK phosphorylation of its serine residues in the catalytic domain. The activated MAPKK is capable of phosphorylating threonine and tyrosine residues in the catalytic domain of a downstream kinase MAPK, thus MAPKK is a dual-specificity kinase. MAPKK is well known as a mediator of Mos-dependent activation of MAPK cascade in maturing oocytes (Kosako et al. 1992 Xiong et al. 2008). 

Two dual specificity kinases are preferentially induced by wild-type rather than by oncogenic RAS-P21 in Xenopus oocytes. Front Biosci 11 2420-2427. 

Qu Y, Adler V, Izotova L, Pestka S, Bowne W, Michl J, Boutjdir M, Friedman FK, Pincus MR. 2007. The dual-specificity kinases, TOPK and DYRKIA, are critical for oocyte maturation induced by wild-type—but not by oncogenic—ras-p21 protein. Front Biosci 12 5089-5097. 

---