Characterization of CKbeta8 and CKbeta8-1: two alternatively spliced forms of human beta-chemokine, chemoattractants for neutrophils, monocytes, and lymphocytes, and potent agonists at CC chemokine receptor 1.
Two new members of human beta-chemokine cDNA were isolated based on structural and functional similarities to human leukotactin-1. One of these clones was identical to the previously isolated human beta-chemokine, CKbeta8, whereas the other is a splicing variant of CKbeta8, therefore named CKbeta8-1. CKbeta8 was short in 51 nucleotides (17 amino acids) compared with CKbeta8-1. The mature proteins of CKbeta8-1 and CKbeta8 consisted of 116 and 99 amino acids with calculated molecular weights of 12,500 and 10,950, respectively. Both CKbeta8-1 and CKbeta8 were potent agonists at CCR1. These chemokines chemoattracted neutrophils, monocytes, and lymphocytes. They also significantly suppressed colony formation by human bone marrow, granulocyte-macrophage, erythroid, and multipotential progenitor cells stimulated by combinations of growth factors. To our knowledge, this is the first example that an alternative splicing produces two active beta-chemokines from a single gene.
Youn
B S
BS
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zhang
S M
SM
Broxmeyer
H E
HE
Cooper
S
S
Antol
K
K
Fraser
M
M
Kwon
B S
BS
D017398:Alternative Splicing; D001483:Base Sequence; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics*; D002634:Chemotaxis, Leukocyte; D002886:Chromosomes, Human, Pair 17; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005796:Genes; D006801:Humans; D007438:Introns; D008214:Lymphocytes / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D019707:Receptors, Chemokine / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D019742:Chemokines, CC; D018076:DNA, Complementary; D019707:Receptors, Chemokine; D002118:Calcium