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© The Rockefeller University Press, 0021-9525/1998//587 $5.00
The Journal of Cell Biology, Volume 142, Number 2, , 1998 587-594

Articles

Integrin {alpha}1β1 Mediates a Unique Collagen-dependent Proliferation Pathway In Vivo



Ambra Pozzi*, Kishore K. Wary{ddagger}, Filippo G. Giancotti{ddagger}, and Humphrey A. Gardner*

* Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037; and {ddagger} Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021

Activation of integrins upon binding to extracellular matrix proteins is believed to be a crucial step for the regulation of cell survival and proliferation. We have used integrin {alpha}1-null mice to investigate the role of this collagen receptor in the regulation of cell growth and survival in vivo. {alpha}1-deficient animals, which are viable and fertile, have a hypocellular dermis and a deficiency in dermal fibroblast proliferation as embryos. In vitro analysis of {alpha}1-null embryonic fibroblasts has revealed that their proliferation rate is markedly reduced when plated on collagenous substrata, despite normal attachment and spreading. Moreover, on the same collagenous matrices, {alpha}1-null fibroblasts fail to recruit and activate the adaptor protein Shc. The failure to activate Shc is accompanied by a downstream deficiency in recruitment of Grb2 and subsequent mitogen-activated protein kinase activation. Taken together with the growth deficiency observed on collagens, this finding indicates that the {alpha}1β1 is the sole collagen receptor which can activate the Shc mediated growth pathway. Thus, integrin {alpha}1 has a unique role among the collagen receptors in regulating both in vivo and in vitro cell proliferation in collagenous matrices.

Key Words: {alpha}1β1 integrin • collagen • proliferation • signal transduction • dermis

Abbreviations used in this paper: BrdU, 5'-bromo-2'-deoxy-uridine; ECM, extracellular matrix; EF, embryonic fibroblasts; MAPK, mitogen-activated protein kinase; PCNA, proliferating cell nuclear antigen.

H. Gardner thanks J. Trotter for training in flow cytometry, and J. Leopard for histotechnology.

Address all correspondence to Humphrey A. Gardner, Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Tel.: (619) 784-9821. Fax: (619) 784-9927. E-mail: humphrey{at}scripps.edu


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