Integrin-associated protein binding domain of thrombospondin-1 enhances insulin-like growth factor-I receptor signaling in vascular smooth muscle cells.
Insulin-like growth factor-I (IGF-I) stimulates vascular smooth muscle cell (SMC) proliferation and migration. The response of smooth muscle cells to IGF-I is determined not only by activation of the IGF-I receptor but also by at least three other transmembrane proteins, alphaVbeta3, integrin-associated protein ( IAP), and SHPS-1. This regulation seems to be attributable to their ability to regulate the transfer of SHP-2 phosphatase, a key component of IGF-I signaling. Ligand occupancy of SHPS-1 with IAP is required for the recruitment and transfer of SHP-2 and subsequent signaling in response to IGF-I. The extracellular matrix protein thrombospondin-1 stimulates an increase in the cell proliferation response to IGF-I. Because thrombospondin-1 is a ligand for IAP, we wished to determine whether the enhancing effect of thrombospondin-1 was mediated through IAP binding. To examine the effect of thrombospondin-1 binding to IAP, we used a peptide termed 4N1K derived from the IAP binding site of thrombospondin-1. Preincubation with 4N1K increased IGF-I-stimulated mitogen-activated protein kinase activation and DNA synthesis. This enhancement seemed to be attributable to its ability to increase the duration of IGF-I-stimulated receptor and insulin receptor substrate-1 (IRS-1) phosphorylation. Preincubation with 4N1K delayed IGF-I stimulation of SHPS-1 phosphorylation (attributable to an alteration in IAP-SHPS-1 interaction), resulting in a delay in SHP-2 recruitment. This delay in SHP-2 transfer seems to account for the increase in the duration of IGF-I receptor phosphorylation and for enhanced downstream signaling. These observations support the conclusion that thrombospondin-1 and IGF-I seem to function coordinately in stimulating smooth muscle proliferation via the thrombospondin-1 interaction with IAP.[1]References
- Integrin-associated protein binding domain of thrombospondin-1 enhances insulin-like growth factor-I receptor signaling in vascular smooth muscle cells. Maile, L.A., Clemmons, D.R. Circ. Res. (2003) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
