title: Truncation of NH2-terminal amino acid residues increases agonistic potency of leukotactin-1 on CC chemokine receptors 1 and 3.
abstract: Leukotactin-1 (Lkn-1) is a human CC chemokine that binds to both CC chemokine receptor 1 (CCR1) and CCR3. Structurally, Lkn-1 is distinct from other human CC chemokines in that it has long amino acid residues preceding the first cysteine at the NH(2) terminus, and contains two extra cysteines. NH(2)-terminal amino acids of Lkn-1 were deleted serially, and the effects of each deletion were investigated. In CCR1-expressing cells, serial deletion up to 20 amino acids (Delta20) did not change the calcium flux-inducing activity significantly. Deletion of 24 amino acids (Delta24), however, increased the agonistic potency approximately 100-fold. Deletion of 27 or 28 amino acids also increased the agonistic potency to the same level shown by Delta24. Deletion of 29 amino acids, however, abolished the agonistic activity almost completely showing that at least 3 amino acid residues preceding the first cysteine at the NH(2) terminus are essential for the biological activity of Lkn-1. Loss of agonistic activity was due to impaired binding to CCR1. In CCR3-expressing cells, Delta24 was the only form of Lkn-1 mutants that revealed increased agonistic potency. Our results indicate that posttranslational modification is a potential mechanism for the regulation of biological activity of Lkn-1.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Jae Kwon
authors.initials: JK
authors.lastname: Lee
authors.forename: Eun Hwa
authors.initials: EH
authors.lastname: Lee
authors.forename: Yeo Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Kyungjae
authors.initials: K
authors.lastname: Kim
authors.forename: KyuBum
authors.initials: K
authors.lastname: Kwack
authors.forename: Doe Sun
authors.initials: DS
authors.lastname: Na
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D019742:Chemokines, CC / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D017931:DNA Primers; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000819:agonists*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology
chemical_list: C515300:CCR1 protein, human; C515350:CCR3 protein, human; D019742:Chemokines, CC; D017931:DNA Primers; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D002118:Calcium