Minireview: Integral membrane proteins that function coordinately with the insulin-like growth factor I receptor to regulate intracellular signaling.
Integral membrane proteins that are present on cell surfaces bind to extracellular ligands, and this binding influences multiple cellular processes. Three cell surface proteins, alpha V beta 3 integrin, integrin associated protein, and SHPS-1, have been shown to modulate both IGF-I receptor-linked signaling and cellular growth and migration responses that are stimulated by IGF-I. Ligand occupancy of these three proteins influences the recruitment of the phosphatase SHP-2 to the IGF-I receptor and thereby modulates the duration of IGF-I receptor tyrosine phosphorylation. In addition, changes in ligand occupancy of these three integral membrane proteins can regulate the transfer of SHP-2 phosphatase to downstream signaling molecules, which is also required for stimulation of cell migration and DNA synthesis by IGF-I. Determination of the spectrum of ligands for these three integral membrane proteins and the mechanisms by which each ligand functions to alter IGF-I signaling are important objectives of future research.
Clemmons
David R
DR
Department of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. dpm@med.unc.edu
Maile
Laura A
LA
D000818:Animals; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000502:physiology; D008024:Ligands; D008565:Membrane Proteins / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D039302:Integrin alphaVbeta3; D016023:Integrins; D008024:Ligands; D008565:Membrane Proteins; D017526:Receptor, IGF Type 1