Pulling on a cytokine

The extracellular matrix (ECM) acts as a storage facility for tons of factors waiting to do business in the cell. Annes et al. (page 723) show that the ECM anchoring of one factor, the cytokine TGF-β, is essential for its activation. The anchoring may give cells something to pull against, with the pulling mediating the activation.

Most TGF-β is secreted as a complex containing TGF-β, a TGF-β pro-domain, and a protein called the latent TGF-β binding protein (LTBP). By the time the complex is extracellular, the pro-domain has been cleaved from TGF-β but remains noncovalently bound to TGF-β and covalently linked (via disulfides) to LTBP. The pro-domain stops TGF-β from signaling, but the complex can be activated in the presence of cells expressing the integrin α_Vβ₆.

The mechanism...