PMID:16079136

2008-04-12T05:39:38Z

66.249.65.19: New PMID: Page!

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<span style = 'font-size: large'> '''Zong, X, Eckert, C, Yuan, H, Wahl-Schott, C, Abicht, H, Fang, L, Li, R, Mistrik, P, Gerstner, A, Much, B, Baumann, L, Michalakis, S, Zeng, R, Chen, Z and Biel, M''' (2005) A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotide-gated channels by Src kinase.''J. Biol. Chem.'' '''280''':34224-32</span>

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|{{TableHeadingColor}} |'''Abstract''' || Hyperpolarization-activated cyclic nucleotide-gated channels (HCN1-4) play a crucial role in the regulation of cell excitability. Importantly, they contribute to spontaneous rhythmic activity in brain and heart. HCN channels are principally activated by membrane hyperpolarization and binding of cAMP. Here, we identify tyrosine phosphorylation by Src kinase as another mechanism affecting channel gating. Inhibition of Src by specific blockers slowed down activation kinetics of native and heterologously expressed HCN channels. The same effect on HCN channel activation was observed in cells cotransfected with a dominant-negative Src mutant. Immunoprecipitation demonstrated that Src binds to and phosphorylates native and heterologously expressed HCN2. Src interacts via its SH3 domain with a sequence of HCN2 encompassing part of the C-linker and the cyclic nucleotide binding domain. We identified a highly conserved tyrosine residue in the C-linker of HCN channels (Tyr476 in HCN2) that confers modulation by Src. Replacement of this tyrosine by phenylalanine in HCN2 or HCN4 abolished sensitivity to Src inhibitors. Mass spectrometry confirmed that Tyr476 is phosphorylated by Src. Our results have functional implications for HCN channel gating. Furthermore, they indicate that tyrosine phosphorylation contributes in vivo to the fine tuning of HCN channel activity.
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|{{TableHeadingColor}} nowrap |'''Links''' || [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16079136 PubMed]
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!Gene product!!Qualifier!!GO ID!!GO term name!!Evidence Code!!with/from!!Aspect!!Notes!!Status
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PMID:15937339

2008-04-11T00:03:54Z

66.249.65.19: New PMID: Page!

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<span style = 'font-size: large'> '''Pereira, CM, Sattlegger, E, Jiang, HY, Longo, BM, Jaqueta, CB, Hinnebusch, AG, Wek, RC, Mello, LE and Castilho, BA''' (2005) IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation.''J. Biol. Chem.'' '''280''':28316-23</span>

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|{{TableHeadingColor}} |'''Abstract''' || Translational control directed by the eukaryotic translation initiation factor 2 alpha-subunit (eIF2alpha) kinase GCN2 is important for coordinating gene expression programs in response to nutritional deprivation. The GCN2 stress response, conserved from yeast to mammals, is critical for resistance to nutritional deficiencies and for the control of feeding behaviors in rodents. The mouse protein IMPACT has sequence similarities to the yeast YIH1 protein, an inhibitor of GCN2. YIH1 competes with GCN2 for binding to a positive regulator, GCN1. Here, we present evidence that IMPACT is the functional counterpart of YIH1. Overexpression of IMPACT in yeast lowered both basal and amino acid starvation-induced levels of phosphorylated eIF2alpha, as described for YIH1 (31). Overexpression of IMPACT in mouse embryonic fibroblasts inhibited phosphorylation of eIF2alpha by GCN2 under leucine starvation conditions, abolishing expression of its downstream target genes, ATF4 (CREB-2) and CHOP (GADD153). IMPACT bound to the minimal yeast GCN1 segment required for interaction with yeast GCN2 and YIH1 and to native mouse GCN1. At the protein level, IMPACT was detected mainly in the brain. IMPACT was found to be abundant in the majority of hypothalamic neurons. Scattered neurons expressing this protein at higher levels were detected in other regions such as the hippocampus and piriform cortex. The abundance of IMPACT correlated inversely with phosphorylated eIF2alpha levels in different brain areas. These results suggest that IMPACT ensures constant high levels of translation and low levels of ATF4 and CHOP in specific neuronal cells under amino acid starvation conditions.
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|{{TableHeadingColor}} nowrap |'''Links''' || [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15937339 PubMed]
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|- {{table heading style}}
!Gene product!!Qualifier!!GO ID!!GO term name!!Evidence Code!!with/from!!Aspect!!Notes!!Status
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|[{{SERVER}}/colipedia/index.php?title=Special:TableEdit&id=63ce1649aab8b3180235b0af7618f667.0.Y47feaae994c72&page=0&pagename={{FULLPAGENAMEE}} edit table] || || || || || || || ||
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EcoliWiki - User contributions [en]

PMID:16079136

PMID:15937339