Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein.

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Citation

Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Lavin MF, Esumi H

Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein.

J Biol Chem. 2003 Jan 3;278(1):48-53. Epub 2002 Oct 29.

PubMed ID
12409306 [ View in PubMed
]
Abstract

We identified a novel human AMP-activated protein kinase (AMPK) family member, designated ARK5, encoding 661 amino acids with an estimated molecular mass of 74 kDa. The putative amino acid sequence reveals 47, 45.8, 42.4, and 55% homology to AMPK-alpha1, AMPK-alpha2, MELK, and SNARK, respectively, suggesting that it is a new member of the AMPK family. It has a putative Akt phosphorylation motif at amino acids 595-600, and Ser(600) was found to be phosphorylated by active Akt resulting in the activation of kinase activity toward the SAMS peptide, a consensus AMPK substrate. During nutrient starvation, ARK5 supported the survival of cells in an Akt-dependent manner. In addition, we also demonstrated that ARK5, when activated by Akt, phosphorylated the ATM protein that is mutated in the human genetic disorder ataxia-telangiectasia and also induced the phosphorylation of p53. On the basis of our current findings, we propose that a novel AMPK family member, ARK5, is the tumor cell survival factor activated by Akt and acts as an ATM kinase under the conditions of nutrient starvation.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Serine-protein kinase ATMQ13315Details
NUAK family SNF1-like kinase 1O60285Details