Open AccessEvidence for an insulin receptor substrate 1 independent insulin signaling pathway that mediates insulin-responsive glucose transporter (GLUT4) translocation.
Author(s) -
Aaron J. Morris,
Stuart S. Martin,
Tetsuro Haruta,
James G. Nelson,
Péter Vollenweider,
Thomas A. Gustafson,
Mike Mueckler,
David W. Rose,
Jerrold M. Olefsky
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.16.8401
Subject(s) - glut4 , insulin receptor , insulin receptor substrate , insulin , irs2 , glucose transporter , irs1 , glucose uptake , phosphotyrosine binding domain , grb10 , medicine , biology , signal transduction , chemistry , microbiology and biotechnology , endocrinology , biochemistry , insulin resistance , sh2 domain , tyrosine phosphorylation
Interaction of the activated insulin receptor (IR) with its substrate, insulin receptor substrate 1 (IRS-1), via the phosphotyrosine binding domain of IRS-1 and the NPXY motif centered at phosphotyrosine 960 of the IR, is important for IRS-1 phosphorylation. We investigated the role of this interaction in the insulin signaling pathway that stimulates glucose transport. Utilizing microinjection of competitive inhibitory reagents in 3T3-L1 adipocytes, we have found that disruption of the IR/IRS-1 interaction has no effect upon translocation of the insulin-responsive glucose transporter (GLUT4). The activity of these reagents was demonstrated by their ability to block insulin stimulation of two distinct insulin bioeffects, membrane ruffling and mitogenesis, in 3T3-L1 adipocytes and insulin-responsive rat 1 fibroblasts. These data suggest that phosphorylated IRS-1 is not an essential component of the metabolic insulin signaling pathway that leads to GLUT4 translocation, yet it appears to be required for other insulin bioeffects.