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PMID:11276227
| Citation |
Fu, AK, Fu, WY, Cheung, J, Tsim, KW, Ip, FC, Wang, JH and Ip, NY (2001) Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction. Nat. Neurosci. 4:374-81 |
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| Abstract |
Here we describe an important involvement of Cdk5/p35 in regulating the gene expression of acetylcholine receptor (AChR) at the neuromuscular synapse. Cdk5 and p35 were prominently expressed in embryonic muscle, and concentrated at the neuromuscular junction in adulthood. Neuregulin increased the p35-associated Cdk5 kinase activity in the membrane fraction of cultured C2C12 myotubes. Co-immunoprecipitation studies revealed the association between Cdk5, p35 and ErbB receptors in muscle and cultured myotubes. Inhibition of Cdk5 activity not only blocked the NRG-induced AChR transcription, but also attenuated ErbB activation in cultured myotubes. In light of our finding that overexpression of p35 alone led to an increase in AChR promoter activity in muscle, Cdk5 activation is sufficient to mediate the up-regulation of AChR gene expression. Taken together, these results reveal the unexpected involvement of Cdk5/p35 in neuregulin signaling at the neuromuscular synapse. |
| Links |
PubMed Online version:10.1038/86019 |
| Keywords |
Animals; Blotting, Western; Brain Chemistry; Cell Fractionation; Cell Line; Chick Embryo; Cyclin-Dependent Kinase 5; Cyclin-Dependent Kinases/metabolism; Embryo, Mammalian/physiology; Gene Expression Regulation; Immunohistochemistry; MAP Kinase Signaling System/physiology; Muscle Development; Muscle, Skeletal/cytology; Muscle, Skeletal/embryology; Muscle, Skeletal/growth & development; Muscle, Skeletal/metabolism; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neuregulins/genetics; Neuregulins/metabolism; Neuromuscular Junction/physiology; Phosphorylation; Precipitin Tests; Rats; Receptor, erbB-2/metabolism; Receptors, Cholinergic/genetics; Receptors, Cholinergic/metabolism; Recombinant Proteins/metabolism; Transfection; Transgenes/genetics |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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