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, Je Sang 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
Externally publishedYes

Fingerprint

Type C Phospholipases
Protein C
Protein Kinase C
Chemical activation
Cyclin D3
CC Chemokines
Proteins
Immediate-Early Genes
Mitogen-Activated Protein Kinase 3
MAP Kinase Signaling System
Protein C Inhibitor
Pertussis Toxin
Gene Expression Regulation
Osteosarcoma
Cells
Cell Differentiation
Cell Cycle
Phosphorylation
Cell Proliferation
Cell proliferation

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKCδ/Ras cascades in HOS cells. / Kim, In Sik; Ryang, Yong Suk; Kim, Yoon Suk; Jang, Sung Wuk; Sung, Ho Joong; Lee, Young Han; Kim, Jiyoung; Na, Doe Sun; Ko, Je Sang.

In: Life Sciences, Vol. 73, No. 4, 13.06.2003, p. 447-459.

Research output: Contribution to journalArticle

Kim, IS, Ryang, YS, Kim, YS, Jang, SW, Sung, HJ, Lee, YH, Kim, J, Na, DS & Ko, JS 2003, 'Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKCδ/Ras cascades in HOS cells', Life Sciences, vol. 73, no. 4, pp. 447-459. https://doi.org/10.1016/S0024-3205(03)00312-6
Kim, In Sik ; Ryang, Yong Suk ; Kim, Yoon Suk ; Jang, Sung Wuk ; Sung, Ho Joong ; Lee, Young Han ; Kim, Jiyoung ; Na, Doe Sun ; Ko, Je Sang. / Leukotactin-1-induced ERK activation is mediated via Gi/Go protein/PLC/PKCδ/Ras cascades in HOS cells. In: Life Sciences. 2003 ; Vol. 73, No. 4. pp. 447-459.
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AU - Jang, Sung Wuk

AU - Sung, Ho Joong

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AU - Kim, Jiyoung

AU - Na, Doe Sun

AU - Ko, Je Sang

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AB - 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.

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