Portal de Periódicos da CAPES

Truncation of NH2-terminal Amino Acid Residues Increases Agonistic Potency of Leukotactin-1 on CC Chemokine Receptors 1 and 3

2002; Elsevier BV; Volume: 277; Issue: 17 Linguagem: Inglês

10.1074/jbc.m109309200

1083-351X

Jae Kwon Lee, Eun Hwa Lee, Yeo Pyo Yun, Kyungjae Kim, KyuBum Kwack, Doe Sun Na, Byoung S. Kwon, Chong‐Kil Lee,

Cell Adhesion Molecules Research

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 (Δ20) did not change the calcium flux-inducing activity significantly. Deletion of 24 amino acids (Δ24), however, increased the agonistic potency ∼100-fold. Deletion of 27 or 28 amino acids also increased the agonistic potency to the same level shown by Δ24. 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, Δ24 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.