PMID- 19333232
OWN - NLM
STAT- MEDLINE
DCOM- 20090617
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 89
IP  - 6
DP  - 2009 Jun
TI  - Pro- and anti-apoptotic dual functions of the C5a receptor: involvement of 
      regulator of G protein signaling 3 and extracellular signal-regulated kinase.
PG  - 676-94
LID - 10.1038/labinvest.2009.27 [doi]
AB  - When apoptosis is initiated by manganese (II) loading, hyperthermia or 
      thapsigargin treatment, human HL-60 and AsPC-1 cells initiate de novo synthesis 
      of the C5a receptor (C5aR) and generation of its ligand, the ribosomal protein 
      S19 (RP S19) homodimer. The ligand-receptor interaction, in an 
      autocrine/paracrine fashion, promotes apoptosis, which can be bypassed by 
      exogenous administration of C5a, another ligand. The proapoptotic function of the 
      RP S19 dimer is reproduced by a C5a/RPS19 chimera that contains the body of C5a 
      and the C-terminal region (Ile134-His145) of RP S19. The RP S19 dimer or 
      C5a/RPS19 and C5a inversely regulate the expression of Regulator of G protein 
      Signaling 3 (RGS3) gene in the apoptosis-initiated cells. Namely, the RP S19-type 
      proteins upregulate RGS3 expression, whereas the C5a reduce it. Transformation of 
      HL-60 cells to overexpress RGS3 promotes apoptosis in association with the 
      downregulation of the Extracellular signal-Regulated Kinase (ERK) signal, and 
      vice versa in the RGS3 knocked-down cells. Consistent with this result, an 
      inhibitor of ERK phosphorylation effectively enhances the apoptotic rate in 
      wild-type HL-60 cells. Moreover, a dominant negative effect on the RP S19 dimer 
      production encourages apoptosis-initiated HL-60 cells with a longer lifespan in 
      mouse than the natural effect. Our data indicate that, in apoptosis-initiated 
      cells, the ligand-dependent C5aR-mediated dual signal affects the fate of cells, 
      either apoptosis execution or survival, through regulation of RGS3 gene 
      expression and subsequent modulation of ERK signal.
FAU - Nishiura, Hiroshi
AU  - Nishiura H
AD  - Department of Molecular Pathology, Faculty of Medical and Pharmaceutical 
      Sciences, Kumamoto University, Kumamoto, Japan. seino@kumamoto-u.ac.jp
FAU - Nonaka, Hideo
AU  - Nonaka H
FAU - Revollo, Ivette S
AU  - Revollo IS
FAU - Semba, Umeko
AU  - Semba U
FAU - Li, Ying
AU  - Li Y
FAU - Ota, Yoshihiko
AU  - Ota Y
FAU - Irie, Atsushi
AU  - Irie A
FAU - Harada, Kumiko
AU  - Harada K
FAU - Kehrl, John H
AU  - Kehrl JH
FAU - Yamamoto, Tetsuro
AU  - Yamamoto T
LA  - eng
GR  - Z01 AI000738/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20090330
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (RGS Proteins)
RN  - 0 (RGS3 protein, human)
RN  - 0 (Receptor, Anaphylatoxin C5a)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (ribosomal protein S19)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cell Line, Tumor
MH  - Chemotaxis, Leukocyte
MH  - Extracellular Signal-Regulated MAP Kinases/*physiology
MH  - Female
MH  - GTP-Binding Proteins/*physiology
MH  - GTPase-Activating Proteins/*physiology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Neoplasm Transplantation
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Multimerization
MH  - RGS Proteins
MH  - Receptor, Anaphylatoxin C5a/agonists/*physiology
MH  - Ribosomal Proteins/metabolism
MH  - Signal Transduction/*physiology
PMC - PMC7503222
MID - NIHMS1621858
EDAT- 2009/04/01 09:00
MHDA- 2009/06/18 09:00
PMCR- 2020/09/21
CRDT- 2009/04/01 09:00
PHST- 2009/04/01 09:00 [entrez]
PHST- 2009/04/01 09:00 [pubmed]
PHST- 2009/06/18 09:00 [medline]
PHST- 2020/09/21 00:00 [pmc-release]
AID - S0023-6837(22)03004-5 [pii]
AID - 10.1038/labinvest.2009.27 [doi]
PST - ppublish
SO  - Lab Invest. 2009 Jun;89(6):676-94. doi: 10.1038/labinvest.2009.27. Epub 2009 Mar 
      30.