Chemokine-like factor 1, a novel cytokine, induces nerve cell migration through the non-extracellular Ca2+-dependent tyrosine kinases pathway.
Chemokine-like factor 1 (CKLF1) is a newly cloned chemotactic cytokine. The roles of CKLF1 in the immune system and the respiratory system have been reported, but its function in the nervous system is still remaining unclear. We aimed to investigate the role of CKLF1 in the nerve cell migration and its regulatory mechanisms. By chemotaxis assays and wound-healing assays, CKLF1 stimulated the migration of SH-SY5Y cells dose-dependently. By immunofluorescence staining, CKLF1 induced actin polymerization. By western blotting, proline-rich tyrosine kinase 2 (PYK2) was phosphorylated at Tyr-402 in response to CKLF1 and this phosphorylation was apparently suppressed by phospholipase C-gamma inhibitor U73122, but not extracellular Ca(2+) chelator EGTA. Furthermore, after transfection of dominant-negative mutant PYK2 plasmid, the chemotaxis upon CKLF1 was significantly attenuated in SH-SY5Y cells. Concluding, CKLF1 stimulates the migration of SH-SY5Y cells dose-dependently by activating non-extracellular Ca(2+)-dependent tyrosine kinases pathway and inducing actin polymerization.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Zhen-Zhen
ZZ
Wang
Gang
G
Li
Xiao-Yu
XY
Chen
Ming
M
Zhao
Yu-He
YH
Yuan
Xiao-Liang
XL
Wang
Nai-Hong
NH
Chen
D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D018925:Chemokines / Q000008:administration & dosage*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D062792:MARVEL Domain-Containing Proteins; D009474:Neurons / Q000187:drug effects*; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014945:Wound Healing / Q000187:drug effects
D000199:Actins; C432676:CKLF protein, human; D018925:Chemokines; D004791:Enzyme Inhibitors; D004963:Estrenes; D062792:MARVEL Domain-Containing Proteins; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D051418:Focal Adhesion Kinase 2; D051966:Phospholipase C gamma; D002118:Calcium