Document Detail


Two C-terminal peptides of human CKLF1 interact with the chemokine receptor CCR4.
MedLine Citation:
PMID:  18069042     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human chemokine-like factor 1 (CKLF1) exhibits chemotactic effects on leukocytes. A previous study demonstrated that CKLF1 is a functional ligand for human CC chemokine receptor 4 (CCR4). In this study, N-terminal amino acid sequencing of secreted CKLF1 protein showed that it contains at least two peptides, C27 and C19. To examine whether C27 or C19 play a role via CCR4, C27 and C19 were chemically synthesized and analyzed by chemotaxis, calcium mobilization, and receptor internalization assays in CCR4-tranfected HEK293 cells or Hut78 cells. The chemotaxis assay showed that C27 could induce chemotaxis to CCR4-transfected HEK293 cells or Hut78 cells while C19 had weaker chemotactic activity, especially in Hut78 cells. C27- or C19-induced chemotaxis was abolished by pertussis toxin, suggesting the involvement of a Gi/o pathway. C27- or C19-induced chemotaxis was also inhibited by an antagonist of CCR4 that show good binding potency, excellent chemotaxis inhibitory activity and selectivity toward CCR4, suggesting that their chemotactic activity specifically involved CCR4. The chemotactic response of CCR4-tranfected HEK293 cells to C27 or C19 was markedly inhibited by preincubation with TARC/CCL17. TARC/CCL17 effectively desensitized the calcium mobilization induced by C27 or C19. Similarly, both of C27 or C19 also desensitized the calcium mobilization and chemotaxis of CCR4-tranfected HEK293 cells in response to TARC/CCL17, suggesting that they might interact with a common receptor. Both C27- and C19-induced clear internalization of CCR4-EGFP. These results confirm that the secreted peptides of CKLF1, C27 and C19, have functional activation via CCR4.
Authors:
Ying Wang; Yingmei Zhang; Wenling Han; Dan Li; Linjie Tian; Caihua Yin; Dalong Ma
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-04
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  40     ISSN:  1357-2725     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2008  
Date Detail:
Created Date:  2008-03-10     Completed Date:  2008-06-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  909-19     Citation Subset:  IM    
Affiliation:
Center for Human Disease Genomics, Peking University, Beijing 100083, PR China.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Calcium / metabolism
Cell Line
Chemokines / chemistry*,  metabolism
Chemotaxis / drug effects
Humans
Molecular Sequence Data
Peptides / chemistry,  pharmacology
Protein Transport
Receptors, CCR4 / metabolism*
Chemical
Reg. No./Substance:
0/CKLF protein, human; 0/Chemokines; 0/Peptides; 0/Receptors, CCR4; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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