Integrin α1β1 mediates a unique collagen-dependent proliferation pathway in vivo Journal Article
| Authors: | Pozzi, A.; Wary, K. K.; Giancotti, F. G.; Gardner, H. A. |
| Article Title: | Integrin α1β1 mediates a unique collagen-dependent proliferation pathway in vivo |
| Abstract: | 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 α1-null mice to investigate the role of this collagen receptor in the regulation of cell growth and survival in vivo. α1-deficient animals, which are viable and fertile, have a hypocellular dermis and a deficiency in dermal fibroblast proliferation as embryos. In vitro analysis of α1-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, α1-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 mitogenactivated protein kinase activation. Taken together with the growth deficiency observed on collagens, this finding indicates that the α1β1 is the sole collagen receptor which can activate the Shc mediated growth pathway. Thus, integrin α1 has a unique role among the collagen receptors in regulating both in vivo and in vitro cell proliferation in collagenous matrices. |
| Keywords: | signal transduction; genetics; nonhuman; cell proliferation; proteins; animal cell; mouse; animal; cytology; metabolism; mouse mutant; animals; mice; mice, knockout; cell survival; cells, cultured; cell division; cell growth; protein; enzyme activation; dermis; physiology; extracellular matrix; skin; cell culture; collagen; immunoprecipitation; fibroblast; adaptor proteins, signal transducing; dna flanking region; antigens, cd; cycline; proliferation; signal transducing adaptor protein; leukocyte antigen; integrin; integrins; grb2 adaptor protein; growth factor receptor bound protein 2; collagen synthesis; vesicular transport adaptor protein; adaptor proteins, vesicular transport; ca(2+)-calmodulin dependent protein kinase; cell spreading; priority journal; article; protein kinase (calcium,calmodulin); alpha1 integrin; src homology 2 domain containing, transforming protein 1; src homology 2 domain-containing, transforming protein 1; α1β1 integrin; grb2 protein, mouse; very late activation antigen 1; integrin alpha1; integrin alpha1beta1 |
| Journal Title: | Journal of Cell Biology |
| Volume: | 142 |
| Issue: | 2 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 1998-07-27 |
| Start Page: | 587 |
| End Page: | 594 |
| Language: | English |
| DOI: | 10.1083/jcb.142.2.587 |
| PUBMED: | 9679154 |
| PROVIDER: | scopus |
| PMCID: | PMC2133043 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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