UMMS Affiliation

Department of Cancer Biology and the Cancer Center

Date

8-4-2004

Document Type

Article

Subjects

1-Phosphatidylinositol 3-Kinase; Animals; Antigens, CD29; Cell Adhesion; Cell Division; Humans; Laminin; Male; Mice; Phosphoproteins; Prostate; Prostatic Neoplasms; Proteins; Receptors, Somatomedin; Signal Transduction

Disciplines

Cancer Biology

Abstract

We show here that beta1 integrins selectively modulate insulin-like growth factor type I receptor (IGF-IR) signaling in response to IGF stimulation. The beta1A integrin forms a complex with the IGF-IR and insulin receptor substrate-1 (IRS-1); this complex does not promote IGF-I mediated cell adhesion to laminin (LN), although it does support IGF-mediated cell proliferation. In contrast, beta1C, an integrin cytoplasmic variant, increases cell adhesion to LN in response to IGF-I and its down-regulation by a ribozyme prevents IGF-mediated adhesion to LN. Moreover, beta1C completely prevents IGF-mediated cell proliferation and tumor growth by inhibiting IGF-IR auto-phosphorylation in response to IGF-I stimulation. Evidence is provided that the beta1 cytodomain plays an important role in mediating beta1 integrin association with either IRS-1 or Grb2-associated binder1 (Gab1)/SH2-containing protein-tyrosine phosphate 2 (Shp2), downstream effectors of IGF-IR: specifically, beta1A associates with IRS-1 and beta1C with Gab1/Shp2. This study unravels a novel mechanism mediated by the integrin cytoplasmic domain that differentially regulates cell adhesion to LN and cell proliferation in response to IGF.

Rights and Permissions

Citation: J Cell Biol. 2004 Aug 2;166(3):407-18. Link to article on publisher's site

DOI of Published Version

10.1083/jcb.200403003

Related Resources

Link to Article in PubMed

Journal Title

The Journal of cell biology

PubMed ID

15289498

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