Prolonged tyrosine kinase activation of insulin receptor by pY27-caveolin-2.
Caveolin-2 regulation of insulin receptor (IR) tyrosine kinase activity was investigated. An insulin time course revealed that rapidly induced tyrosine phosphorylation of IR was steadily maintained over a 180 min time period. In parallel, insulin-exerted IR interaction with caveolin-2 was detected as early as 5 min throughout until 180 min. Down-regulation of caveolin-2 by caveolin-2 siRNA arrested specifically a long term activation of IR. The attenuation of IR activation resulted in retardation of rapamycin-sensitive pS727-STAT3 activation. As caveolin-2 tyrosine mutants were examined, Y27A-caveolin-2 explicitly impeded the long term IR activation by insulin, enhanced tyrosine dephosphorylation of IR, impaired tyrosine phosphorylation of IRS-1, and exerted the interaction between activated IR and SOCS-3. Together, we propose that pY27-caveolin-2 prolongs IR activation by its interaction with IR, thereby preventing IR interaction with SOCS-3.
Kwon
Hayeong
H
Department of Biochemistry, Division of Applied Life Science (BK21 Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Pak
Yunbae
Y
D000818:Animals; D051243:Caveolin 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011972:Receptor, Insulin / Q000096:biosynthesis* / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D051243:Caveolin 2; D055504:Insulin Receptor Substrate Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D014443:Tyrosine; D011972:Receptor, Insulin