Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis.
We report here the molecular cloning of a newly identified preprotachykinin gene, Pptc, which specifies the sequence for a new preprotachykinin protein and bioactive peptide designated hemokinin 1 (HK-1). PPT-C mRNA was detected primarily in hematopoietic cells in contrast to the previously described Ppta and Pptb genes, which are predominantly expressed in neuronal tissues. HK-1 has several biological activities that are similar to the most studied tachykinin, substance P, such as induction of plasma extravasation and mast cell degranulation. However, HK-1 also has properties that are indicative of a critical role in mouse B cell development. HK-1 stimulated the proliferation of interleukin 7-expanded B cell precursors, whereas substance P had no effect. HK-1, but not substance P, promoted the survival of freshly isolated bone marrow B lineage cells or cultured, lipopolysaccharide-stimulated pre-B cells. N-acetyl-L-trytophan-3,5-bistrifluromethyl benzyl ester, a tachykinin receptor antagonist, increased apoptosis of these cells and in vivo administration of this antagonist led to specific reductions of the B220lowCD43 population (the pre-B cell compartment) in the bone marrow and the IgMhighIgDlow population (the newly generated B cells) in the spleen. Thus, HK-1 may be an autocrine factor that is important for the survival of B cell precursors at a critical phase of development.
Zhang
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Y
Ontario Cancer Institute, Princess Margaret Hospital, University Health Network and Department of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada, M5G 2M9.
Lu
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L
Furlonger
C
C
Wu
G E
GE
Paige
C J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015320:Tachykinins / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
D017931:DNA Primers; D018076:DNA, Complementary; D011498:Protein Precursors; D012333:RNA, Messenger; C486037:TAC4 protein, human; C423233:Tac4 protein, mouse; D015320:Tachykinins; C044206:preprotachykinin; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D014364:Tryptophan