Premium
TAO kinases mediate activation of p38 in response to DNA damage
Author(s) -
Raman Malavika,
Earnest Svetlana,
Zhang Kai,
Zhao Yingming,
Cobb Melanie H
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601668
Subject(s) - biology , dna damage , kinase , p38 mitogen activated protein kinases , protein serine threonine kinases , microbiology and biotechnology , dna , genetics , protein kinase a
Thousand and one amino acid (TAO) kinases are Ste20p‐related MAP kinase kinase kinases (MAP3Ks) that activate p38 MAPK. Here we show that the TAO kinases mediate the activation of p38 in response to various genotoxic stimuli. TAO kinases are activated acutely by ionizing radiation, ultraviolet radiation, and hydroxyurea. Full‐length and truncated fragments of dominant negative TAOs inhibit the activation of p38 by DNA damage. Inhibition of TAO expression by siRNA also decreases p38 activation by these agents. Cells in which TAO kinases have been knocked down are less capable of engaging the DNA damage‐induced G2/M checkpoint and display increased sensitivity to IR. The DNA damage kinase ataxia telangiectasia mutated (ATM) phosphorylates TAOs in vitro ; radiation induces phosphorylation of TAO on a consensus site for phosphorylation by the ATM protein kinase in cells; and TAO and p38 activation is compromised in cells from a patient with ataxia telangiectasia that lack ATM. These findings indicate that TAO kinases are regulators of p38‐mediated responses to DNA damage and are intermediates in the activation of p38 by ATM.