Regulator of G protein signaling 1 suppresses CXCL12-mediated migration and AKT activation in RPMI 8226 human plasmacytoma cells and plasmablasts

Hyo-Kyung Pak; Minchan Gil; Yoonkyung Lee; Hyunji Lee; A-Neum Lee; Jin Roh; Chan-Sik Park

doi:10.1371/journal.pone.0124793

Regulator of G protein signaling 1 suppresses CXCL12-mediated migration and AKT activation in RPMI 8226 human plasmacytoma cells and plasmablasts

PLoS One. 2015 Apr 21;10(4):e0124793. doi: 10.1371/journal.pone.0124793. eCollection 2015.

Authors

Hyo-Kyung Pak¹, Minchan Gil², Yoonkyung Lee², Hyunji Lee², A-Neum Lee², Jin Roh³, Chan-Sik Park⁴

Affiliations

¹ Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
² Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea.
³ Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁴ Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea; Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

Migration of plasma cells to the bone marrow is critical factor to humoral immunity and controlled by chemokines. Regulator of G protein signaling 1 (RGS1) is a GTPase-activating protein that controls various crucial functions such as migration. Here, we show that RGS1 controls the chemotactic migration of RPMI 8226 human plasmacytoma cells and human plasmablasts. LPS strongly increased RGS1 expression and retarded the migration of RPMI 8226 cells by suppressing CXCL12-mediated AKT activation. RGS1 knockdown by siRNA abolished the retardation of migration and AKT suppression by LPS. RGS1-dependent regulation of migration via AKT is also observed in cultured plasmablasts. We propose novel functions of RGS1 that suppress AKT activation and the migration of RPMI 8226 cells and plasmablasts in CXCL12-mediated chemotaxis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemokine CXCL12 / genetics*
Chemokine CXCL12 / metabolism
Chemotaxis / drug effects
Gene Expression Regulation
Humans
Lipopolysaccharides / pharmacology
Plasma Cells / drug effects*
Plasma Cells / metabolism
Plasma Cells / pathology
Plasmacytoma / genetics
Plasmacytoma / metabolism*
Plasmacytoma / pathology
Proto-Oncogene Proteins c-akt / genetics*
Proto-Oncogene Proteins c-akt / metabolism
RGS Proteins / antagonists & inhibitors
RGS Proteins / genetics*
RGS Proteins / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction
Tumor Cells, Cultured

Substances

CXCL12 protein, human
Chemokine CXCL12
Lipopolysaccharides
RGS Proteins
RGS1 protein, human
RNA, Small Interfering
Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by the National Research Foundation of Korea, Grant No 2008-0062286, to C-SP (http://www.nrf.re.kr/) and the Asan Institute for Life Sciences, grant no. 2011-0794 to C-SP (http://en.ails.amc.seoul.kr/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.