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PMID: 11284715 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Identification and characterization of a novel sucrose-non-fermenting protein kinase/AMP-activated protein kinase-related protein kinase, SNARK.

The Biochemical journal ·Vol. 355 ·No. Pt 2 ·2001-04-15 ·Pages 297-305

Lefebvre DL, Bai Y, Shahmolky N, Sharma M, Poon R, Drucker DJ, Rosen CF

Abstract

Subtraction hybridization after the exposure of keratinocytes to ultraviolet radiation identified a differentially expressed cDNA that encodes a protein of 630 amino acid residues possessing significant similarity to the catalytic domain of the sucrose-non-fermenting protein kinase (SNF1)/AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. Northern blotting and reverse-transcriptase-mediated PCR demonstrated that mRNA transcripts for the SNF1/AMPK-related kinase (SNARK) were widely expressed in rodent tissues. The SNARK gene was localized to human chromosome 1q32 by fluorescent in situ hybridization. SNARK was translated in vitro to yield a single protein band of approx. 76 kDa; Western analysis of transfected baby hamster kidney (BHK) cells detected two SNARK-immunoreactive bands of approx. 76-80 kDa. SNARK was capable of autophosphorylation in vitro; immunoprecipitated SNARK exhibited phosphotransferase activity with the synthetic peptide substrate HMRSAMSGLHLVKRR (SAMS) as a kinase substrate. SNARK activity was significantly increased by AMP and 5-amino-4-imidazolecarboxamide riboside (AICAriboside) in rat keratinocyte cells, implying that SNARK might be activated by an AMPK kinase-dependent pathway. Furthermore, glucose deprivation increased SNARK activity 3-fold in BHK fibroblasts. These findings identify SNARK as a glucose- and AICAriboside-regulated member of the AMPK-related gene family that represents a new candidate mediator of the cellular response to metabolic stress.

MeSH Terms
Adenosine Monophosphate/pharmacology Amino Acid Sequence Aminoimidazole Carboxamide/analogs & derivatives,pharmacology Animals Base Sequence Cells, Cultured Chromosome Mapping Cricetinae DNA, Complementary Enzyme Activation Glucose/metabolism Humans Hydrogen-Ion Concentration Molecular Sequence Data Phosphorylation Precipitin Tests Protein Serine-Threonine Kinases/chemistry,genetics,metabolism RNA, Messenger/genetics Rats Ribonucleotides/pharmacology Sequence Homology, Amino Acid Substrate Specificity
Chemicals
DNA, Complementary RNA, Messenger Ribonucleotides Aminoimidazole Carboxamide Adenosine Monophosphate Nuak2 protein, rat NUAK2 protein, human Protein Serine-Threonine Kinases AICA ribonucleotide Glucose
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lefebvre D L
Department of Medicine, Division of Dermatology, Toronto General Hospital, Banting Institute, Room 317, 100 College Street, Toronto M5G 1L5, Ontario, Canada.
Bai Y
Shahmolky N
Sharma M
Poon R
Drucker D J
Rosen C F
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/0264-6021:3550297
Published
2001-04-15
Pages
297-305
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1221739
Subset
IM
External Links
PubMed source DOI: 10.1042/0264-6021:3550297 PMC Full Text View journal details
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