Heparin is essential for a single keratinocyte growth factor molecule to bind and form a complex with two molecules of the extracellular domain of its receptor.

Keratinocyte growth factor (KGF or FGF-7) is a member of the heparin binding fibroblast growth factor (FGF) family and is a paracrine mediator of proliferation and differentiation of a wide variety of epithelial cells. To examine the stoichiometry of complexes formed between KGF and its receptor, we have utilized a soluble variant of the extracellular region of the KGF receptor containing two tandem immunoglobulin-like loops, loops II and III (sKGFR). Ligand-receptor complexes were examined by size exclusion chromatography, light scattering, N-terminal protein sequencing, and sedimentation velocity.

Mutation of Cys672 allows recombinant expression of activatible macrophage-stimulating protein.

We readily produced recombinant pro-macrophage stimulating protein in a mammalian expression system, but it was only weakly active after proteolytic activation. Active macrophage stimulating protein is a disulfide-bonded heterodimer, but in our hands, the subunits of recombinant macrophage stimulating protein were mostly not disulfide bonded. Molecular modeling of the serine proteinase domain of macrophage stimulating protein based on homology to human trypsin suggested that macrophage stimulating protein, but not plasminogen or hepatocyte growth factor, has a Cys residue (672) in close proximity to the Cys residue (578) that forms the intersubunit disulfide link with the other subunit.

A novel intracellular epithelial cell tyrosine kinase is expressed in the skin and gastrointestinal tract.

A portion of the catalytic domain of a novel tyrosine kinase was cloned from mouse intestinal crypt cells, in a screen designed to identify kinases that may play a role in the regeneration of the intestinal epithelium (E Siyanova, MS Serfas, IA Mazo and AL Tyner, Oncogene 9, 2053-2057). We have cloned a cDNA encoding this kinase, termed sik for src-related intestinal kinase. The sik cDNA encodes a 451 amino acid protein that shares 80% identity with the recently cloned human tyrosine kinase, brk.

Formation of mitogenically active PDGF-B dimer does not require interchain disulfide bonds.

Platelet-derived growth factor (PDGF), a major mitogen for mesenchymal cells, is a disulfide-bonded dimer of two subunit polypeptides named A and B. All of the three possible dimeric forms, i.e.