Hemokinin is a hematopoietic-specific tachykinin that regulates B lymphopoiesis

Abstract

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.

Substance P Regulates Th1-Type Colitis in IL-10 Knockout Mice

“…Another tachykinin, neurokinin B, comes from preprotachykinin B, which is encoded by a different gene (murine tachykinin 2 or human tachykinin 3). Yet another tachykinin gene, tachykinin 4, produces preprotachykinin c and a novel tachykinin called hemokinin (35).…”

“…SP and hemokinin bind NK-1R with high affinity (36). However, hemokinin may signal somewhat differently from SP and may have some separate functions (35). Most reports suggest that the other tachykinins bind either NK-2R or NK-3R with high affinity and are low affinity agonists of NK-1R.…”

Characterization of the endokinins: Human tachykinins with cardiovascular activity

“…Evidence of a fourth mammalian tachykinin, hemokinin 1 (HK-1), encoded on TAC4 and expressed in the hematopoietic cells of mice has been demonstrated (11). This tachykinin is uniquely expressed outside of neuronal tissue in immune tissues (11).…”

“…This tachykinin is uniquely expressed outside of neuronal tissue in immune tissues (11). It has subsequently been found to be a full agonist at the NK 1 , NK 2 , and NK 3 receptors, with highest selectivity for NK 1 (12,13).…”

Pain regulation of endokinin A/B or endokinin C/D on chimeric peptide MCRT in mice

“…Their biological activities were mediated primarily through three receptors denoted NK 1 , NK 2 and NK 3 that belong to the G protein-coupled receptor (GPCR) superfamily (Maggi 1995;Nakanishi 1991;Pennefather et al 2004). Four novel mammalian tachykinins, endokinins A, B, C and D (EKA -D), were encoded on a new human preprotachykinin gene homologous to TAC4 gene identified in mice and rats (Kurtz et al 2002;Page et al 2003;Zhang et al 2000). EKA/B (the common C-terminal decapeptide in EKA and EKB) shared a characteristic carboxyl-terminal FXGLM-NH 2 motif, while EKC/D (the common C-terminal duodecapeptide in EKC and EKD) possessed an untypical region, FQGLL-NH 2 (Page et al 2003).…”