Comparison of the signaling abilities of the cytoplasmic domains of the insulin receptor and the insulin receptor-related receptor in 3T3-L1 adipocytes.
In the present work a chimeric receptor containing the intracellular domain of the insulin receptor-related receptor (IRR) and the extracellular domain of the colony stimulating factor-1 (CSF-1) receptor was expressed in 3T3-L1 adipocytes and compared with the parallel chimeric receptor containing the cytoplasmic domain of the insulin receptor (IR). Both chimeric receptors exhibited CSF-stimulated tyrosine kinase activity when assayed in vitro after in vivo activation comparable to that of the endogenous IR present in these cells. No cross-activation of the expressed chimeric and endogenous receptors was observed. The cytoplasmic domain of the IRR was found to 1) mediate activation of the Ser/Thr kinase Akt/PKB, 2) stimulate glucose uptake, 3) inhibit lipolysis, and 4) stimulate glycogen synthase, all with a potency comparable to those of the expressed CSF-1R/IR chimera and the endogenous insulin receptors. These results indicate that despite the extensive differences in sequence between the cytoplasmic domains of the IRR and IR, the elements required for insulin-specific responses have been conserved in this distinct member of the insulin receptor family.
Department of Molecular Pharmacology, Stanford University School of Medicine, California 94305, USA.
A A
AA
Dandekar
B J
BJ
Wallach
A
A
Barthel
R A
RA
Roth
D016475:3T3 Cells / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction
D007328:Insulin; D011993:Recombinant Fusion Proteins; D016173:Macrophage Colony-Stimulating Factor; D006006:Glycogen Synthase; D011972:Receptor, Insulin; C066542:insulin receptor-related receptor; D017346:Protein Serine-Threonine Kinases; D005947:Glucose