BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein

@article{citeulike:2717446, abstract = {Transforming growth factor {beta}1 (TGF{beta}1), an important regulator of cell behavior, is secreted as a large latent complex (LLC) in which it is bound to its cleaved prodomain (latency-associated peptide [LAP]) and, via LAP, to latent TGF{beta}-binding proteins (LTBPs). The latter target LLCs to the extracellular matrix (ECM). Bone morphogenetic protein 1 (BMP1)-like metalloproteinases play key roles in ECM formation, by converting precursors into mature functional proteins, and in morphogenetic patterning, by cleaving the antagonist Chordin to activate BMP2/4. We provide in vitro and in vivo evidence that BMP1 cleaves LTBP1 at two specific sites, thus liberating LLC from ECM and resulting in consequent activation of TGF{beta}1 via cleavage of LAP by non-BMP1-like proteinases. In mouse embryo fibroblasts, LAP cleavage is shown to be predominantly matrix metalloproteinase 2 dependent. TGF{beta}1 is a potent inducer of ECM formation and of BMP1 expression. Thus, a role for BMP1-like proteinases in TGF{beta}1 activation completes a novel fast-forward loop in vertebrate tissue remodeling. 10.1083/jcb.200606058}, author = {Ge, Gaoxiang and Greenspan, Daniel S. }, citeulike-article-id = {2717446}, doi = {http://dx.doi.org/10.1083/jcb.200606058}, journal = {J. Cell Biol.}, keywords = {bone\_formation}, month = {October}, number = {1}, pages = {111--120}, posted-at = {2008-04-25 12:32:43}, priority = {2}, title = {BMP1 controls TGF{beta}1 activation via cleavage of latent TGF{beta}-binding protein}, url = {http://dx.doi.org/10.1083/jcb.200606058}, volume = {175}, year = {2006} }

TY - JOUR ID - citeulike:2717446 L3 - citeulike-article-id:2717446 TI - BMP1 controls TGF{beta}1 activation via cleavage of latent TGF{beta}-binding protein JF - J. Cell Biol. VL - 175 IS - 1 SP - 111 EP - 120 N2 - Transforming growth factor {beta}1 (TGF{beta}1), an important regulator of cell behavior, is secreted as a large latent complex (LLC) in which it is bound to its cleaved prodomain (latency-associated peptide [LAP]) and, via LAP, to latent TGF{beta}-binding proteins (LTBPs). The latter target LLCs to the extracellular matrix (ECM). Bone morphogenetic protein 1 (BMP1)-like metalloproteinases play key roles in ECM formation, by converting precursors into mature functional proteins, and in morphogenetic patterning, by cleaving the antagonist Chordin to activate BMP2/4. We provide in vitro and in vivo evidence that BMP1 cleaves LTBP1 at two specific sites, thus liberating LLC from ECM and resulting in consequent activation of TGF{beta}1 via cleavage of LAP by non-BMP1-like proteinases. In mouse embryo fibroblasts, LAP cleavage is shown to be predominantly matrix metalloproteinase 2 dependent. TGF{beta}1 is a potent inducer of ECM formation and of BMP1 expression. Thus, a role for BMP1-like proteinases in TGF{beta}1 activation completes a novel fast-forward loop in vertebrate tissue remodeling. 10.1083/jcb.200606058 KW - bone_formation AU - Ge, Gaoxiang AU - Greenspan, Daniel PY - 2006/10/09/ UR - http://dx.doi.org/10.1083/jcb.200606058 ER -