TAO kinases mediate activation of p38 in response to DNA damage.

Article Details


Raman M, Earnest S, Zhang K, Zhao Y, Cobb MH

TAO kinases mediate activation of p38 in response to DNA damage.

EMBO J. 2007 Apr 18;26(8):2005-14. Epub 2007 Mar 29.

PubMed ID
17396146 [ View in PubMed

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.

DrugBank Data that Cites this Article

NameUniProt ID
Serine/threonine-protein kinase TAO2Q9UL54Details
Serine/threonine-protein kinase TAO1Q7L7X3Details
Serine/threonine-protein kinase TAO3Q9H2K8Details