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Cutting Edge |
-Chain of the Hepatocyte Growth Factor/Scatter Factor1
Department of Pathology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030
Pre-pro-B cell growth-stimulating factor (PPBSF) is a
heterodimer of IL-7 and a 30-kDa cofactor. Unlike monomeric IL-7, PPBSF
selectively induces proliferation and differentiation of pre-pro-B
cells and up-regulates IL-7R
-chain expression. Here we clone the
PPBSF cofactor from bone marrow stromal cells and identify it as a
variant 
-chain of hepatocyte growth factor (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
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 cytokine (hybrid cytokine) consisting of the bioactive
components of two unrelated cytokines. Based on its heparin-binding and
mitogenic properties, we postulate that the HGF-chain in PPBSF
enables IL-7 to participate in cognate interactions at the stromal cell
surface and to transduce signals effectively at low levels of
IL-7R.
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