Cutting edge: Identification of a hybrid cytokine consisting of IL-7 and the beta-chain of the hepatocyte growth factor/scatter factor

Pre-pro-B cell growth-stimulating factor (PPBSF) is a heterodimer of IL-7 a nd a 30-kDa cofactor. Unlike monomeric IL-7, PPBSF selectively induces prol iferation and differentiation of pre-pro-B cells and up-regulates IL-7R alp ha -chain expression. Here we clone the PPBSF cofactor from bone marrow str omal cells and identify it as a variant beta -chain of hepatocyte growth fa ctor (HGF), a pleiotropic cytokine homologous to plasminogen that regulates cell growth, motility, and morphogenesis. We further demonstrate that, in the presence of low m.w. heparin sulfate-derived oligosaccharides, rHGF bet a combines with rIL-7 to form a biologically active heterodimer having the properties of PPBSF. The results indicate that PPBSF is a novel form of cyt okine (hybrid cytokine) consisting of the bioactive components of two unrel ated cytokines. Based on its heparin-binding and mitogenic properties, we p ostulate that the HGF beta -chain in PPBSF enables IL-7 to participate in c ognate interactions at the stromal cell surface and to transduce signals ef fectively at low levels of IL-7R.