Efficient Association of an Amino-terminally Extended Form of Human Latent Transforming Growth Factor- Binding Protein with the Extracellular Matrix

doi:10.1074/jbc.270.52.31294

Efficient Association of an Amino-terminally Extended Form of Human Latent Transforming Growth Factor- Binding Protein with the Extracellular Matrix (*)

From the Ludwig Institute for Cancer Research, Box 595, Biomedical Center, S-751 24 Uppsala, Sweden

^¶ To whom correspondence should be addressed. Tel.: 46-18-174146; Fax: 46-18-506867.

↵^§ Present address: Dept. of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, Kami-Ikebukuro 1-37-1, Toshima-ku, Tokyo 170, Japan.

Abstract

Latent transforming growth factor-β (TGF-β) binding protein-1 (LTBP-1) is a component of the high molecular weight latent TGF-β complex found in various cells, including human platelets. LTBP-1 is observed as different molecular sizes in different cell types, probably due to proteolytic processing and alternative splicing. We here report a novel form of human LTBP-1, which is longer in its NH²-terminal part (LTBP-1L). Northern hybridization analysis revealed that the LTBP-1L is derived from a 7.0-kilobase mRNA, whereas the originally reported shorter form (LTBP-1S) is derived from a 5.2-kilobase mRNA. Transfection of cDNA for LTBP-1L and −1S in COS cells revealed that LTBP-1L bound more efficiently to the extracellular matrix than did LTBP-1S. These results suggest that the different splice forms of LTBP-1 mediate different localization patterns of the latent TGF-β complexes in vivo.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank (TM)/EMBL Data Bank with accession number(s) L48925.
↵⁽¹⁾ The abbreviations used are:

TGF-β

transforming growth factor-β

EGF

epidermal growth factor

HEL

human erythroleukemia

LAP

latency-associated peptide

LTBP

latent TGF-β binding protein

LTBP-1L

long form of LTBP-1

LTBP-1S

short form of LTBP-1

PCR

polymerase chain reaction

kb

kilobase(s)

Ab

antibody.
↵⁽²⁾ In order to clarify the nomenclature for members in the growing family of latent TGF-β binding proteins, we have renamed latent TGF-β binding protein (LTBP) as latent TGF-β binding protein-1 (LTBP-1) to indicate that this was the first member of this family to be identified.
↵⁽³⁾ A. Olofsson, unpublished data.
- Received July 5, 1995.
- Revision received October 18, 1995.