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First published online December 31, 2008

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Keeping (TGFβ) active with integrins

Before its activation, the multipotent cytokine TGFβ is secreted from the cell in a latent complex with its inhibitory peptide LAP. Two integrin heterodimers, vβ6 and vβ8, activate the TGFβ isoforms TGFβ1 and TGFβ3 in vivo, dislodging LAP by interacting with an Arg-Gly-Asp (RGD) sequence on the latent complex. Six other integrin heterodimers are also known to bind to RGD sequences – but do they activate TGFβ1 and TGFβ3? To address this question, John Munger and colleagues (p. 227) explore the phenotype of mice that lack functional β6- and β8-integrins. The authors first show that double-knockout (Itgb6^–/–/Itgb8^–/–) mice mostly die at mid-gestation. Notably, however, those that survive develop cleft palates – as do Tgfb3^–/– mice. To study the role of integrins vβ6 and vβ8 at later developmental stages, the authors next treat Itgb8^–/– mice with an anti-vβ6-integrin antibody after palate fusion. These mice develop severe systemic autoimmunity (indicated by mononuclear infiltrates in several organs) and also lack Langerhans cells, echoing the phenotype of mice that lack integrin-responsive TGFβ1. The authors propose, therefore, that the activity of integrins vβ6 and vβ8 (but not of other RGD-binding integrins) is required for the developmental effects of TGFβ1 and TGFβ3. Their data clarify the role of integrin-mediated TGFβ activation in vivo.

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Mice that lack activity of vβ6- and vβ8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice

Poshala Aluwihare, Zhenyu Mu, Zhicheng Zhao, Dawen Yu, Paul H. Weinreb, Gerald S. Horan, Shelia M. Violette, and John S. Munger
JCS 2009 122: 227-232. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?