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The Journal of Immunology, 2001, 167: 3550-3554.
Copyright © 2001 by The American Association of Immunologists

Cutting Edge

Cutting Edge: Identification of a Hybrid Cytokine Consisting of IL-7 and the {beta}-Chain of the Hepatocyte Growth Factor/Scatter Factor1

Laijun Lai and Irving Goldschneider2

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{alpha}-chain expression. Here we clone the PPBSF cofactor from bone marrow stromal cells and identify it as a variant {beta}-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{beta} 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{beta}-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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