Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein. 1240 6

SNARK, the fourth member of the AMPK catalytic subunit family, was originally identified in a rat kidney cDNA library, and in this study we isolated its human homologue. A BLAST search analysis using rat SNARK protein yielded a single high homology clone, DKFZp434J037, isolated from human testis, and since its hypothetical protein showed 84% homology to rat SNARK protein, we assumed DKFZp434J037 to be the human SNARK cDNA. The human SNARK cDNA is 3443bp long and encodes a 628 amino acid protein having an estimated molecular weight of 69kDa, and its chromosomal localization had been assigned to 1q32.1. The same as other members of AMPK catalytic subunit family, human SNARK showed AMP-dependent GST-SAMS phosphorylation activity and enhanced HepG2 cell survival during glucose starvation. Human SNARK-overexpressing HepG2 cells (H/SNK) showed acute cell-cell detachment when exposed to glucose-free medium and the cell-cell detachment correlated well with the detection of G-actin. Deletion mutant analysis strongly suggested that the putative catalytic domain of SNARK is necessary for the cell-cell detachment, and Western blotting analysis showed that phosphorylation of FAK and PKC, which were dramatically increased by glucose starvation in HepG2 cells, was markedly suppressed by SNARK.
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PMID:Induction of cell-cell detachment during glucose starvation through F-actin conversion by SNARK, the fourth member of the AMP-activated protein kinase catalytic subunit family. 1457 7