IRS-2, but not IRS-1, can sustain proliferation and rescue UBF stabilization in InR or InR defective signaling of 32D myeloid cells.
Despite both IRS-1 and IRS-2 are two important adaptor molecules essential for intracellular signaling of insulin and IGF-I, the distinct biological pattern of IRS-2 versus IRS-1 remains as a concernful issue to be clarified. We demonstrated here an important evidence that in 32D myeloid cells expressing the insulin receptor (InR) or selected mutants of the InR, IRS-2, but not IRS-1, is required for promoting the proliferation and inhibiting the granulocytic differentiation, thus restore ERKs phosphorylation and UBF1 stabilization. In addition, unlike IRS-1, IRS-2 can effectively compensate the InR defective signaling and lead to the activation of cell cycle progression and proliferation genes in 32D myeloid cells. These results indicate a predominant role of IRS-2 involved in InR signaling of 32D myeloid cells.
Wu
Shufang
S
School of Medicine of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Zhou
Bo
B
Xu
Lin
L
Sun
Hongzhi
H
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction
D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; D035463:Pol1 Transcription Initiation Complex Proteins; C063844:transcription factor UBF; D019938:Cyclin D1; D011972:Receptor, Insulin; D048049:Extracellular Signal-Regulated MAP Kinases