Gene Set: MULLIGAN_NTF3_SIGNALING_VIA_INSR_AND_IGF1R_UP

Standard name MULLIGAN_NTF3_SIGNALING_VIA_INSR_AND_IGF1R_UP
Systematic name M1593
Brief description Genes similarly up-regulated in 3T3-L1 cells (fibroblasts able to differentiate to adipocytes) upon stimulation of INSR or IGFR1 by NTF3 [GeneID=3643;3480;4908].
Full description or abstract Insulin and insulin-like growth factor-1 (IGF-1) act through highly homologous receptors that engage similar intracellular signaling pathways, yet these hormones serve largely distinct physiological roles in the control of metabolism and growth, respectively. In an attempt to uncover the molecular mechanisms underlying their divergent functions, we compared insulin receptor (IR) and IGF-1 receptor (IGF-1R) regulation of gene expression by microarray analysis, using 3T3-L1 cells expressing either TrkC/IR or TrkC/IGF-1R chimeric receptors to ensure the highly selective activation of each receptor tyrosine kinase. Following stimulation of the chimeric receptors for 4 h, we detected 11 genes to be differentially regulated, of which 10 were up-regulated to a greater extent by the IGF-1R. These included genes involved in adhesion, transcription, transport, and proliferation. The expression of mRNA encoding heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen, was markedly increased by IGF-1R but not IR activation. This effect was dependent on MAPK, but not phosphatidylinositol 3-kinase, and did not require an autocrine loop through the epidermal growth factor receptor. HB-EGF mitogenic activity was detectable in the medium of 3T3-L1 preadipocytes expressing activated IGF-1R but not IR, indicating that the transcriptional response is accompanied by a parallel increase in mature HB-EGF protein. The differential abilities of the IR and IGF-1R tyrosine kinases to stimulate the synthesis and release of a growth factor may provide, at least in part, an explanation for the greater role of the IGF-1R in the control of cellular proliferation.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 12213819   Authors: Mulligan C,Rochford J,Denyer G,Stephens R,Yeo G,Freeman T,Siddle K,O'Rahilly S
Exact source Table 1A
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Organism Mus musculus
Contributed by John Newman (University of Washington)
Source platform MOUSE_SEQ_ACCESSION
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Version history 3.1: First introduced

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