Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKCδ/Ras cascades in HOS cells

In Sik Kim, Yong Suk Ryang, Yoon Suk Kim, Sung Wuk Jang, Ho Joong Sung, Young Han Lee, Jiyoung Kim, Doe Sun Na, Jesang Ko

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Recently cloned leukotactin-1 (Lkn-1) that belongs to CC chemokine family has not been characterized. To understand the intracellular events following Lkn-1 binding to CCR1, we investigated the activities of signaling molecules in response to Lkn-1 in human osteogenic sarcoma cells expressing CCR1. Lkn-1-stimulated cells showed elevated phosphorylation of extracellular signal-related kinases (ERK1/2) with a distinct time course. ERK activation was peaked in 30 min and 12 h showing biphasic activation of ERK. Pertussis toxin, an inhibitor of Gi/Go protein, and phospholipase C (PLC) inhibitor blocked Lkn-1-induced activation of ERK. Protein kinase Cδ (PKCδ) specific inhibitor rottlerin inhibited ERK activation in Lkn-1-stimulated cells. The activities of PLC and PKCδ were also enhanced by Lkn-1 stimulation. Dominant negative Ras inhibited activation of ERK. Immediate early response genes such as c-fos and c-myc were induced by Lkn-1 stimulation. Lkn-1 affected the cell cycle progression by cyclin D3 induction. These results suggest that Lkn-1 activates the ERK pathway by transducing the signal through Gi/Go protein, PLC, PKCδ and Ras, and it may play a role for cell proliferation, differentiation, and regulation of gene expression for other cellular processes.

Original languageEnglish
Pages (from-to)447-459
Number of pages13
JournalLife Sciences
Volume73
Issue number4
DOIs
Publication statusPublished - 2003 Jun 13

Keywords

  • CCR1
  • Chemokine
  • ERK
  • Leukotactin-1
  • PKC
  • PLC
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Kim, I. S., Ryang, Y. S., Kim, Y. S., Jang, S. W., Sung, H. J., Lee, Y. H., Kim, J., Na, D. S., & Ko, J. (2003). Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKCδ/Ras cascades in HOS cells. Life Sciences, 73(4), 447-459. https://doi.org/10.1016/S0024-3205(03)00312-6