The integrin αvβ8 mediates epithelial homeostasis through MT1-MMP–dependent activation of TGF-β1

Journal of Cell Biology - Tập 157 Số 3 - Trang 493-507 - 2002
Dezhi Mu1,2,3, Stephanie Cambier1,2, Lars Fjellbirkeland1,2, Jody L. Baron4, John S. Munger5, Hisaaki Kawakatsu2, Dean Sheppard1,2, V. Courtney Broaddus1,2, Stephen L. Nishimura1,2
12University of California at San Francisco/Mt. Zion Cancer Center, University of California at San Francisco, San Francisco, CA 94143
25The Lung Biology Center and Pulmonary Division, San Francisco General Hospital, San Francisco, CA 94110
3Department of Pathology, University of California at San Francisco/Mt. Zion Cancer Center, San Francisco, CA 94143, USA.
43Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143
54Department of Medicine and Cell Biology, New York University, New York, NY 10016

Tóm tắt

Întegrins, matrix metalloproteases (MMPs), and the cytokine TGF-β have each been implicated in homeostatic cell behaviors such as cell growth and matrix remodeling. TGF-β exists mainly in a latent state, and a major point of homeostatic control is the activation of TGF-β. Because the latent domain of TGF-β1 possesses an integrin binding motif (RGD), integrins have the potential to sequester latent TGF-β (SLC) to the cell surface where TGF-β activation could be locally controlled. Here, we show that SLC binds to αvβ8, 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-β, 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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Journal of Cell Biology

Tập 157 Số 3

493-507

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