Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The SNF1 protein kinase is required for the regulatory response to glucose starvation in Saccharomyces cerevisiae. SNF1 is a protein serine/threonine kinase that has been widely conserved in both plants and mammals. Previously, we identified SIP1 and SIP2 as proteins that interact with SNF1 in vivo by the two-hybrid system. We have cloned the SIP2 gene and the encoded protein is homologous to SIP1 and to GAL83, which affects glucose repression of the GAL genes. We show that SIP2 and GAL83, like SIP1, co-immunoprecipitate with SNF1 and are phosphorylated in vitro. An 80 amino acid sequence, designated the ASC domain, is highly conserved at the C-termini of all three proteins. We show that this small domain can mediate protein-protein interaction with the SNF1 kinase complex. Thus, SIP1, SIP2 and GAL83 define a family of homologous proteins that are tightly associated with the SNF1 kinase, probably in alternative forms of the complex. Genetic evidence suggests that the three proteins have distinct, but related, functions in the SNF1 pathway, and deletion of GAL83 dramatically reduces SNF1 activity in immune complex assays. We propose that SIP1, SIP2 and GAL83 act as adaptors that promote the activity of SNF1 towards specific targets.
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PMID:A family of proteins containing a conserved domain that mediates interaction with the yeast SNF1 protein kinase complex. 781 28

Expression of the GAL genes of Saccharomyces cerevisiae is subject to glucose repression, a global regulatory mechanism that requires several gene products. We have isolated GAL83, one of these genes required for glucose repression. The sequence of the predicted Gal83 protein is homologous to two other yeast proteins, Sip1p and Sip2p, which are known to interact with the SNF1 gene product, a protein kinase required for expression of the GAL genes. High-copy clones of SIP1 and SIP2 cross-complement the GAL83-2000 mutation (as well as GAL82-1, a mutation in another gene involved in glucose repression), suggesting that these four genes may perform similar functions in glucose repression. Consistent with this hypothesis, a gal83 null mutation does not affect glucose repression, and only dominant or partially dominant mutations exist in GAL83 (and GAL82). Two other observations were made that suggests that GAL83 functions interdependently with GAL82 and REG1 (another gene involved in glucose repression) to effect glucose repression: 1) REG1 on a low-copy plasmid cross-complements GAL82-1 and GAL83-2000 mutations, and 2) all pairwise combinations of reg1, GAL82-1 and GAL83-2000 fail to complement one another. Such unlinked noncomplementation suggests that Gal83p, Gal82p and Reg1p may interact with one another. Possible roles for GAL83, GAL82 and REG1 are discussed in relation to SNF1, SIP1 and SIP2.
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PMID:Genetic and molecular characterization of GAL83: its interaction and similarities with other genes involved in glucose repression in Saccharomyces cerevisiae. 829 71

There is growing evidence that mammalian AMP-activated protein kinase (AMPK) plays a role in protecting cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. The active form of AMPK from rat liver exists as a heterotrimeric complex and we have previously shown that the catalytic subunit is structurally and functionally related to the SNF1 protein kinase from Saccharomyces cerevisiae. Here we describe the isolation and characterization of the two other polypeptides, termed AMPKbeta and AMPKgamma, that together with the catalytic subunit (AMPKalpha) form the active kinase complex in mammalian liver. Sequence analysis of cDNA clones encoding these subunits reveals that they are related to yeast proteins that interact with SNF1, providing further evidence that the regulation and function of AMPK and SNF1 have been conserved throughout evolution. The amino acid sequence of the beta subunit is most closely related to SIP2 (35% identity), while the amino acid sequence of the gamma subunit is 35% identical with SNF4. We show that both AMPKbeta and AMPKgamma mRNA and protein are expressed widely in rat tissues. We show that AMPKbeta interacts with both AMPKalpha and AMPKgamma in vitro, whereas AMPKalpha does not interact with AMPKgamma under the same conditions. These results suggest that AMPKbeta mediates the association of the heterotrimeric AMPK complex in vitro, and will facilitate future studies aimed at investigating the regulation of AMPK in vivo.
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PMID:Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro. 862 96

StubSNF1 is a potato cDNA that encodes a protein kinase similar to the yeast SNF1 gene involved in transcriptional regulation of glucose-repressible genes. The yeast SNF1 functions in a complex with GAL83/SIP1/SIP2 and SNF4 proteins. We have used StubSNF1 as bait in a yeast two-hybrid system to screen for potato cDNAs encoding proteins that bind to StubSNF1. Three overlapping cDNAs, two different in size, were isolated. DNA sequence analysis revealed that they were orthologues of the yeast GAL83/SIP1/SIP2 genes and their mammalian counterparts, AMPK beta-subunits. The direct interaction between the potato proteins StubGAL83 and StubSNF1 was shown by an in vitro binding assay. Southern and Northern hybridisations revealed that StubGAL83 exists in a low copy number in the potato genome and is highly (but organ-specifically) expressed in potato. In contrast, StubSNF1 possesses low transcript levels in each organ, except in flowers where high amounts of StubSNF1 mRNA could be detected. We demonstrate here that StubGAL83 can also interact with yeast SNF4 in a yeast two-hybrid system suggesting that plant SNF1 kinases may function in complexes similar to those detected in yeast and mammals.
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PMID:Potato StubSNF1 interacts with StubGAL83: a plant protein kinase complex with yeast and mammalian counterparts. 1020 10

Sucrose nonfermenting 1 catalytic subunit (SNF1)-type protein kinases are members of a metabolite-sensing protein kinase family distributed ubiquitously from yeast to plants and animals. In yeast cells, SNF1 acts in complex with the activator subunit SNF4 and a member of the SIP1/SIP2/GAL83 family responsible for substrate definition. The potato (Solanum tuberosum) genome possesses at least two SnRK1s, designated PKIN1 and StubSNF1. In this study, potato kinase 1 (PKIN1) and StubSNF1 were analysed in the yeast two-hybrid system and characterised by suppression of yeast mutations. It was shown that StubSNF1 interacted with the GAL83 ortholog of potato, StubGAL83, and complemented the Delta snf1 mutation. Moreover, it suppressed Delta snf4 and Delta sip1,Delta sip2,Delta gal83 deficiencies. In contrast, PKIN1 was unable to interact with StubGAL83 and did not rescue the yeast mutants. These data suggest different functions for PKIN1 and StubSNF1 in potato.
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PMID:Functional diversity of potato SNF1-related kinases tested in Saccharomyces cerevisiae. 1463 99