Ndr protein kinase is regulated by phosphorylation on two conserved sequence motifs
Ndr protein kinase is regulated by phosphorylation on two conserved sequence motifs
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DOI：
10.1074/jbc.274.48.33847
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发表时间：
1999-11-26
影响因子：
4.8
通讯作者：
Hemmings, BA
中科院分区：
文献类型：
--
作者：
Millward, TA;Hess, D;Hemmings, BA
Ndr is a nuclear serine/threonine protein kinase that belongs to a subfamily of kinases implicated in the regulation of cell division and cell morphology, This subfamily includes the kinases LATS, Orb6, Cot-1, and Dbf2, We show here that Ndr is potently activated when intact cells are treated with okadaic acid, suggesting that Ndr is normally held in a state of low activity by protein phosphatase 2A. We mapped the regulatory phosphorylation sites of Ndr protein kinase and found that active Ndr is phosphorylated on Ser-281 and Thr-444, Mutation of either site to alanine strongly reduced both basal and okadaic acid-stimulated Ndr activity, while combined mutation abolished Ndr activity completely. Importantly, each of these sites (and also the surrounding sequences) are conserved in the kinase relatives of Ndr, suggesting a general mechanism of activation for kinases of this subfamily. Ser-281 and Thr-444 are also similar to the regulatory phosphorylation sites in several targets of the phosphoinositide-dependent protein kinase PDK1.(1) However, PDK1 does not appear to function as an upstream kinase for Ndr, Thus, Ndr and its close relatives may operate in a novel signaling pathway downstream of an as-yet-unidentified kinase with specificity similar to, but distinct from, PDK1.
