CKbeta8/CCL23 and its isoform CKbeta8-1 induce up-regulation of cyclins via the G(i)/G(o) protein/PLC/PKCdelta/ERK leading to cell-cycle progression.
CKbeta8/CCL23 is a CC chemokine and alternative splicing of the CKbeta8 gene produces two mRNAs that encode CKbeta8 and its isoform CKbeta8-1. Chemokines play a critical role in leukocyte trafficking and development of inflammation and chemokines are also known to be involved in cell proliferation. To investigate participation of CKbeta8 and CKbeta8-1 in cell proliferation, we examined the effects of CKbeta8 and CKbeta8-1 in the cell cycle. Both CKbeta8 and CKbeta8-1 induced cell-cycle progression. We next investigated whether MAPKs are involved in CKbeta8- and CKbeta8-1-induced cell proliferation. CKbeta8- and CKbeta8-1-stimulated cells showed phosphorylation of ERK1/2 and an inhibitor study indicated that CKbeta8- and CKbeta8-1-induced activation of ERK1/2 is mediated by the G(i)/G(o) protein, PLC, and PKCdelta. CKbeta8 and CKbeta8-1 regulated expression of the cell cycle regulators cyclin D(3) and cyclin B(1,) and the immediate early response gene products c-Myc and Egr-1. These results indicate that both CKbeta8 and CKbeta8-1 are involved in cell proliferation by modulating the cell cycle regulators.
Kim
Jeonghan
J
Korea University, Seoul, South Korea.
Kim
Yoon Suk
YS
Ko
Jesang
J
D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019742:Chemokines, CC / Q000494:pharmacology*; D016213:Cyclins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D017781:Genes, Immediate-Early; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000494:pharmacology; D051745:Protein Kinase C-delta / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
C105504:CCL23 protein, human; D019742:Chemokines, CC; D016213:Cyclins; D020033:Protein Isoforms; D051745:Protein Kinase C-delta; D048049:Extracellular Signal-Regulated MAP Kinases; D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go