Furthermore, these peptides share the same conserved hydrophobic carboxyl-terminal (C-terminal) region, Phe–X–Gly–Leu–Met–NH2, which is central

to the activation of each of three mammalian tachykinin receptors. In contrast, in the amino-terminal (N-terminal) region, they possess divergent and hydrophilic regions believed to convey receptor specificity, whereby SP shows the highest affinity for NK1, NKA for NK2 and NKB for NK3 receptor [17], [18] and [19]. Namely, it seems likely that NK1, NK2 and NK3 receptors are receptors of SP, NKA and NKB, respectively. In 2000, this consensus had to be changed after the discovery of a fourth mammalian tachykinin in mice [20]. A new cDNA molecule was identified from an mRNA differential display for isolating new growth and differentiation factors involved in mouse Epacadostat clinical trial B cell development [20]. The cloned cDNA had an open reading frame encoding a peptide of 128 amino acids with a 15 amino acid region, Lys–Arg–Ser–Arg–Thr–Arg–Gln–Phe–Tyr–Gly–Leu–Met–Gly–Lys–Arg, that is similar to tachykinin peptides, since this region possesses all the sequence information necessary for the liberation and maturation of a tachykinin peptide. Specifically, the basic Lys–Arg doublets at each end are typical cleavage sites,

and the Gly residue adjacent to the COOH-terminal Met residue provides the NH2 group for COOH-terminal amidation of the mature tachykinin peptide. The pentapeptide sequence Phe–Tyr–Gly–Leu–Met matches the tachykinin signature motif Phe–X–Gly–Leu–Met. Thus, it was OTX015 nmr suggested that the cDNA molecule is a new mouse preprotachykinin gene, mPPT-C (mTAC4), and the putative tachykinin peptide

encoded by mTAC4 was named hemokinin-1 (HK-1), because this gene was restrictedly expressed in hematopoietic cells, and the structure 2-hydroxyphytanoyl-CoA lyase of HK-1 was proposed as Arg–Ser–Arg–Thr–Arg–Gln–Phe–Tyr–Gly–Leu–Met–NH2 (Table 1) [20]. Subsequently, the rat TAC4 encoding a precursor protein of 170 amino acids was identified. This precursor protein encoding a rat HK-1 peptide (rHK-1) displayed 76% identity to that of the mouse (mHK-1) and the amino acid sequence of rHK-1 was identical to that of mHK-1, so it was named rat/mouse hemokinin (r/mHK-1) [21]. Similarly, cDNA encoding a precursor protein of 98 amino acids was identified from human hypothalamic and thymus DNA and was designated human preprotachykinin C (hPPT-C, hTAC4)) [21]. The putative peptide encoded by hTAC4 was also homologous to that of mTAC4; however, unlike the mTAC4 gene in which dibasic cleavage sites flank the predicted HK-1 peptide, the putative peptide encoded by hTAC4 contained two potential monobasic cleavage sites (Lys) in the N-terminal region, Lys–Thr–Gly–Lys–Ala–Ser–Gln–Phe–Phe–Gly–Leu–Met–Gly–Lys–Arg.