Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors.

A novel M. 17,000 heparin-binding protein was purified from culture medium conditioned by A431 human epidermoid carcinoma cells.This protein, designated HBpl7, was found to bind the heparin-binding peptide growth factors HBGF-1 and HBGF-2 in a noncovalent, reversible manner.In addition HBpl7 was found to inhibit the biological activities of both HBGF-1 and HBGF-2.Both the binding and inactivation of HBGF-1 and HBGF-2 by HBpl7 were abolished by heparin.Full-length 1163-base pair HBpl7 cDNA was cloned and sequenced by using the polymerase chain reaction technique.The deduced primary structure of HBpl7 consisted of 234 amino acids including each of five partial peptide sequences obtained from proteolytic fragments of purified HBpl7.The encoded protein included a 33-residue N-terminal signal sequence for secretion and a single potential N-linked glycosylation site.No homology with any known protein was found for the deduced primary structure of HBpl7.The expression of HBpl7 mRNA was found to occur preferentially in normal human keratinocytes and in squamous cell carcinomas.This pattern of HBpl7 gene expression suggests that this binding protein for HBGFs 1 and 2 has a physiological role in squamous epithelia.Heparin-binding growth factors (HBGF)' are a family of seven polypeptide growth factors that include HBGF-1 (acidic FGF), HBGF-2 (basic FGF), K-FGF, Int-2, FGF-5, KGF, and FGF-7 (1-3).Of these HBGF-1 and HBGF-2 have been implicated in a number of biological processes in vitro and in vivo such as growth stimulation of mesodermal-and neuroec- todermal-derived cells, angiogenesis, wound healing, and tis-