PMID- 35551672
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2045-3701 (Print)
IS  - 2045-3701 (Electronic)
IS  - 2045-3701 (Linking)
VI  - 12
IP  - 1
DP  - 2022 May 12
TI  - Analysis of CCR2 splice variant expression patterns and functional properties.
PG  - 59
LID - 10.1186/s13578-022-00787-6 [doi]
LID - 59
AB  - BACKGROUND: C-C motif chemokine receptor 2 (CCR2), the main receptor for monocyte 
      chemoattractant protein-1 (MCP-1), is expressed on immune cells, including 
      monocytes, macrophages, and activated T cells, and mediates cell migration toward 
      MCP-1 in inflammation-related diseases. The CCR2 gene encodes two isoforms: CCR2A 
      and CCR2B. The CCR2B open reading frame is localized in a single exon, similar to 
      other chemokine receptors, and CCR2A and CCR2B feature different amino acid 
      sequences in their C-terminal intracellular loops due to alternative splicing. 
      Most biochemical studies on CCR2-related cellular responses in the immune system 
      have focused on CCR2B, with few reports focused on CCR2A. Understanding the 
      functional properties of CCR2A in cellular responses may elucidate the roles 
      played by MCP-1 and CCR2 in pathophysiological responses. RESULTS: CCR2 gene 
      expression analysis in several cell types revealed that most adherent cells only 
      expressed CCR2A, whereas CCR2B expression was dominant in monocytic cells. The 
      C-terminal Helix 8 region of CCR2A contains few basic amino acids, which may be 
      unfavorable for cell surface localization, as confirmed with the HiBiT assay. 
      CCR2B contains many C-terminal Ser/Thr residues, similar to other chemokine 
      receptors, which may be phosphorylated by G protein-coupled receptor kinases 
      (GRKs) to promote beta-arrestin recruitment and subsequent endocytosis. By contrast, 
      CCR2A contains few C-terminal Ser/Thr residues, which are unlikely to be 
      phosphorylated by GRKs. CCR2A localized on the cell surface is resistant to 
      internalization, despite the interaction between Gbeta and GRKs induced by ligand 
      binding with CCR2A. CCR2A induced cellular responses at a relatively higher 
      degree than CCR2B, although both receptors mediated signaling events through Galphaq 
      and Galphai. HeLa cells lacking CCR2A showed slowed growth compared with parent 
      cells, regardless of MCP-1 stimulation, and their chemotactic activity toward 
      MCP-1, in addition to basal motility, was significantly impaired. CONCLUSION: 
      MCP-1 and CCR2 may play pivotal roles in cancer progression by recruiting 
      macrophages into cancer tissue. This study demonstrates that CCR2A but not CCR2B 
      is expressed in solid cancer-derived cells. CCR2A is resistant to internalization 
      by beta-arrestin due to a distinct C-terminal region from CCR2B, which enhances 
      MCP-1-stimulated responses, indicating that CCR2A may play essential roles in 
      solid cancer progression.
CI  - (c) 2022. The Author(s).
FAU - Park, Hee-Kyung
AU  - Park HK
AD  - Department of Biomedical Sciences, College of Medicine, Korea University, 73 
      Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
FAU - Na, Yun Hee
AU  - Na YH
AD  - Department of Biomedical Sciences, College of Medicine, Korea University, 73 
      Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
FAU - Nguyen, Huong Thi
AU  - Nguyen HT
AD  - Department of Biomedical Sciences, College of Medicine, Korea University, 73 
      Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
FAU - Nguyen, Lan Phuong
AU  - Nguyen LP
AD  - Department of Biomedical Sciences, College of Medicine, Korea University, 73 
      Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
FAU - Hurh, Sunghoon
AU  - Hurh S
AD  - Department of Biomedical Sciences, College of Medicine, Korea University, 73 
      Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
FAU - Seong, Jae Young
AU  - Seong JY
AD  - Department of Biomedical Sciences, College of Medicine, Korea University, 73 
      Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
FAU - Lee, Cheol Soon
AU  - Lee CS
AD  - Department of Biomedical Sciences, College of Medicine, Korea University, 73 
      Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
FAU - Ham, Byung-Joo
AU  - Ham BJ
AD  - Department of Psychiatry, College of Medicine, Korea University, 73 Goryeodae-ro, 
      Seongbuk-gu, Seoul, 02841, Republic of Korea.
FAU - Hwang, Jong-Ik
AU  - Hwang JI
AUID- ORCID: 0000-0002-0729-1782
AD  - Department of Biomedical Sciences, College of Medicine, Korea University, 73 
      Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. hjibio@korea.ac.kr.
LA  - eng
GR  - NRF-2019R1A2C1090051/Ministry of Science and ICT/
GR  - 2020M3E5D9080165/Ministry of Science and ICT/
PT  - Journal Article
DEP - 20220512
PL  - England
TA  - Cell Biosci
JT  - Cell & bioscience
JID - 101561195
PMC - PMC9102224
OTO - NOTNLM
OT  - CCR2
OT  - Chemotaxis
OT  - MCP-1
OT  - Splice variant
OT  - beta-Arrestin
COIS- The authors declare that they have no competing interests.
EDAT- 2022/05/14 06:00
MHDA- 2022/05/14 06:01
PMCR- 2022/05/12
CRDT- 2022/05/13 13:45
PHST- 2022/01/09 00:00 [received]
PHST- 2022/04/12 00:00 [accepted]
PHST- 2022/05/13 13:45 [entrez]
PHST- 2022/05/14 06:00 [pubmed]
PHST- 2022/05/14 06:01 [medline]
PHST- 2022/05/12 00:00 [pmc-release]
AID - 10.1186/s13578-022-00787-6 [pii]
AID - 787 [pii]
AID - 10.1186/s13578-022-00787-6 [doi]
PST - epublish
SO  - Cell Biosci. 2022 May 12;12(1):59. doi: 10.1186/s13578-022-00787-6.