Akyrin repeat and SOCS box containing protein 4 (Asb-4) interacts with GPS1 (CSN1) and inhibits c-Jun NH2-terminal kinase activity
| Autor: | John B. Ammori, Michael W. Mulholland, Weizhen Zhang, Ji Yao Li, Biao Xin Chai, Yi Qing Liu |
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| Rok vydání: | 2007 |
| Předmět: |
Insulin Receptor Substrate Proteins
Immunoprecipitation Recombinant Fusion Proteins Suppressor of Cytokine Signaling Proteins Biology Article Cell Line Mice Phosphoserine Two-Hybrid System Techniques Animals Humans Phosphorylation Sequence Deletion Neurons Arc (protein) Ubiquitin Kinase HEK 293 cells Intracellular Signaling Peptides and Proteins JNK Mitogen-Activated Protein Kinases Cell Biology Phosphoproteins Molecular biology Ankyrin Repeat Rats Transport protein IRS1 Protein Transport Protein Binding |
| Zdroj: | Cellular Signalling. 19:1185-1192 |
| ISSN: | 0898-6568 |
| Popis: | Asb-4 is a gene that is specifically expressed in the hypothalamic energy homeostasis-associated areas and is down-regulated in the arcuate nucleus of fasted Sprague Dawley and obese Zucker rats. It has two functional domains, the ankyrin repeat and the SOCS box. The function of Asb-4 is unclear. We used yeast two hybridization to search for protein(s) that interact with Asb-4. With Asb-4 minus its SOCS box (Asb-4/Deltasb) as a bait, we screened mouse testis and arcuate nucleus cDNA libraries and identified G-protein pathway suppressor 1 (GPS1, also known as CSN1) as an Asb-4 interacting protein. GPS1 co-immunoprecipitated with Asb-4 both in vitro and in human HEK293 cells. When Asb-4 and GPS1 were co-transfected into HEK293 cells, expression of Asb-4 reduced the protein level of GPS1. Deletion of the SOCS box (Asb4/Deltasb) did not abolish the inhibitory effect of Asb-4 on GPS1, indicating that the SOCS box was not needed for its inhibitory effect. In NIH 3T3 L1 cells, expression of GPS1 enhanced c-Jun NH2-terminal kinase (JNK) activity. Co-expression of Asb-4 with GPS1 inhibited JNK activity. Treatment of the cells with insulin (20 nM) stimulated JNK activity. Expression of GPS1 potentiated the stimulatory effect of insulin, whereas co-expression of Asb-4 along with GPS1 inhibited JNK activity. In HEK293 cells expression of GPS1 elevated phosphorylation of insulin receptor substrate 1 (IRS-1) at serine307, co-expression of Asb-4 with GPS1 reduced the IRS-1ser307 phosphorylation. The present study demonstrates that Asb-4 interacts with GPS1 and inhibits JNK activity. |
| Databáze: | OpenAIRE |
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