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J. Cell Biol.,
Volume 142, Number 2, July 27, 1998 587-594
1
1 Mediates a Unique Collagen-dependent
Proliferation Pathway In Vivo
* Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037; and 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 Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York,
10021
1-null mice to investigate the
role of this collagen receptor in the regulation of cell
growth and survival in vivo. 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 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, 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 1
1 is the sole collagen receptor which can activate the Shc mediated growth
pathway. Thus, integrin 1 has a unique role among the
collagen receptors in regulating both in vivo and in
vitro cell proliferation in collagenous matrices.
11 integrin;
collagen;
proliferation;
signal transduction;
dermis
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