Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein.
Latent transforming growth factor beta-binding protein 1 (LTBP-1) targets latent complexes of transforming growth factor beta to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. Fibrillins are extracellular matrix macromolecules whose primary function is architectural: fibrillins assemble into ultrastructurally distinct microfibrils that are ubiquitous in the connective tissue space. LTBPs and fibrillins are highly homologous molecules, and colocalization in the matrix of cultured cells has been reported. To address whether LTBP-1 functions architecturally like fibrillins, microfibrils were extracted from tissues and analyzed immunochemically. In addition, binding studies were conducted to determine whether LTBP-1 interacts with fibrillins. LTBP-1 was not detected in extracted beaded-string microfibrils, suggesting that LTBP-1 is not an integral structural component of microfibrils. However, binding studies demonstrated interactions between LTBP-1 and fibrillins. The binding site was within three domains of the LTBP-1 C terminus, and in fibrillin-1 the site was defined within four domains near the N terminus. Immunolocalization data were consistent with the hypothesis that LTBP-1 is a fibrillin-associated protein present in certain tissues but not in others. In tissues where LTBP-1 is not expressed, LTBP-4 may substitute for LTBP-1, because the C-terminal end of LTBP-4 binds equally well to fibrillin. A model depicting the relationship between LTBP-1 and fibrillin microfibrils is proposed.
Isogai
Zenzo
Z
Department of Biochemistry and Molecular Biology, Shriners Hospital for Children, Oregon Health and Science University, Portland 97239, USA.
Ono
Robert N
RN
Ushiro
Shin
S
Keene
Douglas R
DR
Chen
Yan
Y
Mazzieri
Roberta
R
Charbonneau
Noe L
NL
Reinhardt
Dieter P
DP
Rifkin
Daniel B
DB
Sakai
Lynn Y
LY
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D017364:Collagenases / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000071838:Fibrillin-1; D000071837:Fibrillins; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007313:Insecta; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008024:Ligands; D051379:Mice; D020894:Microfibrils / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008954:Models, Biological; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D054392:Adipokines
D002352:Carrier Proteins; D017364:Collagenases; D018076:DNA, Complementary; D000071838:Fibrillin-1; D000071837:Fibrillins; D019791:Guanidine; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008024:Ligands; D008840:Microfilament Proteins; D011994:Recombinant Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse; C509032:LTBP1 protein, human; C509040:LTBP4 protein, human; C509033:Ltbp1 protein, mouse