Identification and characterization of LTBP-2, a novel latent transforming growth factor-beta-binding protein.
Latent transforming growth factor-beta (TGF-beta)-binding protein (LTBP) is a component of the latent TGF-beta complex in human platelets. LTBP is composed of two different cysteine-rich repeat sequences, i.e. epidermal growth factor (EGF)-like repeats and a repeat containing 8 cysteine residues. The overall structure of LTBP is similar to those of the microfibrillar proteins fibrillin-1 and fibrillin-2. Here we report the identification of a novel protein termed LTBP-2, which is structurally related to LTBP. cDNA for LTBP-2 was obtained from human foreskin fibroblast cDNA libraries using a fragment of the LTBP cDNA as a probe. LTBP-2 is composed of 20 EGF-like repeats and four copies of the 8-cysteine repeat. The amino acid sequence of LTBP-2 is 41% identical to that of LTBP and 25% identical to that of fibrillin-1. LTBP-2 is synthesized as a 240-kDa protein by human foreskin fibroblasts and also by COS cells transfected with the isolated LTBP-2 cDNA. Similar to LTBP, a considerable part of LTBP-2 was found to be associated with extracellular matrix. Co-transfection of cDNAs for LTBP-2 and TGF-beta 1 revealed that LTBP-2 forms a high molecular weight complex with the TGF-beta 1 precursor. The LTBP-2 gene was assigned to chromosome 14q24. These results indicate that different forms of latent TGF-beta complexes occur and suggest that the different associated proteins may function to target the complexes to specific sites.
Morén
A
A
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Olofsson
A
A
Stenman
G
G
Sahlin
P
P
Kanzaki
T
T
Claesson-Welsh
L
L
ten Dijke
P
P
Miyazono
K
K
Heldin
C H
CH
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D053779:Latent TGF-beta Binding Proteins; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; C509035:LTBP2 protein, human; D053779:Latent TGF-beta Binding Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta