PMID- 17015622
OWN - NLM
STAT- MEDLINE
DCOM- 20061128
LR  - 20220318
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 175
IP  - 1
DP  - 2006 Oct 9
TI  - BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein.
PG  - 111-20
AB  - Transforming growth factor beta1 (TGFbeta1), 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 
      TGFbeta-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 TGFbeta1 via cleavage of LAP by non-BMP1-like proteinases. In mouse 
      embryo fibroblasts, LAP cleavage is shown to be predominantly matrix 
      metalloproteinase 2 dependent. TGFbeta1 is a potent inducer of ECM formation and 
      of BMP1 expression. Thus, a role for BMP1-like proteinases in TGFbeta1 activation 
      completes a novel fast-forward loop in vertebrate tissue remodeling.
FAU - Ge, Gaoxiang
AU  - Ge G
AD  - Department of Pathology and Laboratory Medicine, University of Wisconsin School 
      of Medicine and Public Health, Madison, WI 53706, USA.
FAU - Greenspan, Daniel S
AU  - Greenspan DS
LA  - eng
GR  - R01 GM071679/GM/NIGMS NIH HHS/United States
GR  - R01 GM71679/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20061002
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Latent TGF-beta Binding Proteins)
RN  - 0 (Ltbp1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.19 (BMP1 protein, human)
RN  - EC 3.4.24.19 (Bmp1 protein, mouse)
RN  - EC 3.4.24.19 (Bone Morphogenetic Protein 1)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 1
MH  - Bone Morphogenetic Proteins/chemistry/metabolism/*physiology
MH  - Humans
MH  - Latent TGF-beta Binding Proteins/*metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Metalloendopeptidases/chemistry/metabolism/*physiology
MH  - Mice
MH  - Models, Biological
MH  - Protein Structure, Tertiary
MH  - Transforming Growth Factor beta1/*metabolism
PMC - PMC2064503
EDAT- 2006/10/04 09:00
MHDA- 2006/12/09 09:00
PMCR- 2007/04/09
CRDT- 2006/10/04 09:00
PHST- 2006/10/04 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/10/04 09:00 [entrez]
PHST- 2007/04/09 00:00 [pmc-release]
AID - jcb.200606058 [pii]
AID - 200606058 [pii]
AID - 10.1083/jcb.200606058 [doi]
PST - ppublish
SO  - J Cell Biol. 2006 Oct 9;175(1):111-20. doi: 10.1083/jcb.200606058. Epub 2006 Oct 
      2.