Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells.
Leukotactin-1 (Lkn-1)/CCL15 is a recently cloned CC-chemokine that binds to the CCR1 and CCR3. Although Lkn-1 has been known to function as a chemoattractant for neutrophils, monocytes and lymphocytes, its cellular mechanism remains unclear. To understand the mechanism of Lkn-1-induced chemotaxis signaling, we examined the chemotactic activities of human osteogenic sarcoma cells expressing CCR1 in response to Lkn-1 using inhibitors of signaling molecules. Inhibitors of G(i)/G(o) protein, phospholipase C (PLC) and protein kinase Cdelta (PKCdelta) inhibited the chemotactic activity of Lkn-1 indicating that Lkn-1-induced chemotaxis signal is transduced through G(i)/G(o) protein, PLC and PKCdelta. The activities of PLC and PKCdelta were also enhanced by Lkn-1 stimulation. Chemotactic activity of Lkn-1 was inhibited by the treatment of cycloheximide and actinomycin D suggesting that newly synthesized proteins are needed for chemotaxis. Nuclear factor-kappaB (NF-kappaB) inhibitor reduced chemotactic activity of Lkn-1. DNA binding activity of NF-kappaB was also enhanced by Lkn-1 stimulation. These results suggest that Lkn-1 transduces the signal through G(i)/G(o) protein, PLC, PKCdelta, NF-kappaB and newly synthesized proteins for chemotaxis.
Ko
Jesang
J
Immunomodulation Research Center, University of Ulsan, 680-749, Ulsan, South Korea.
Kim
In Sik
IS
Jang
Sung Wuk
SW
Lee
Young Han
YH
Shin
Soon Young
SY
Min
Do Sik
DS
Na
Doe Sun
DS
D002465:Cell Movement / Q000187:drug effects; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D016328:NF-kappa B / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051745:Protein Kinase C-delta; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
C108814:CCL15 protein, human; C515300:CCR1 protein, human; D019742:Chemokines, CC; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins