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 and a 30-kDa cofactor. Unlike monomeric IL-7, PPBSF selectively induces proliferation and differentiation of pre-pro-B cells and up-regulates IL-7Ralpha-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, rHGFbeta 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 HGFbeta-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.
Lai
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Department of Pathology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Goldschneider
I
I
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000737:chemistry* / Q000494:pharmacology; D003001:Cloning, Molecular; D019281:Dimerization; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D015851:Interleukin-7; D021122:Protein Subunits; D012333:RNA, Messenger; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor