期刊
JOURNAL OF CELL BIOLOGY
卷 157, 期 3, 页码 493-507出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200109100
关键词
integrins; transforming growth factor beta; metalloprotease; cell cycle; homeostasis
类别
资金
- NCI NIH HHS [CA63143] Funding Source: Medline
- NHLBI NIH HHS [HL8985, F32 HL008985, HL63786, R01 HL053949, R01 HL063993, HL53949, R37 HL053949, HL63993, R01 HL063786] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
Integrins, matrix metalloproteases (MMPs), and the cytokine TGF-beta have each been implicated in homeostatic cell behaviors such as cell growth and matrix remodeling. TGF-beta exists mainly in a latent state, and a major point of homeostatic control is the activation of TGF-beta. Because the latent domain of TGF-beta1 possesses an integrin binding motif (RGD), integrins have the potential to sequester latent TGF-beta (SLC) to the cell surface where TGF-beta activation could be locally controlled. Here, we show that SLC binds to alphavbeta8, an integrin expressed by normal epithelial and neuronal cells in vivo. This binding results in the membrane type 1 (MT1)-MMP-dependent release of active TGF-beta, which leads to autocrine and paracrine effects on cell growth and matrix production. These data elucidate a novel mechanism of cellular homeostasis achieved through the coordination of the activities of members of three major gene families involved in cell-matrix interactions.
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