PMID- 10629036
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 20
IP  - 3
DP  - 2000 Feb
TI  - Normal hematopoiesis and inflammatory responses despite discrete signaling
      defects in Galpha15 knockout mice.
PG  - 797-804
AB  - Galpha15 activates phospholipase Cbeta in response to the greatest variety of
      agonist-stimulated heptahelical receptors among the four Gq class G-protein alpha
      subunits expressed in mammals. Galpha15 is primarily expressed in hematopoietic
      cells in fetal and adult mice. We disrupted the Galpha15 gene by homologous
      recombination in embryonic stem cells to identify its biological functions.
      Surprisingly, hematopoiesis was normal in Galpha15(-/-) mice, Galpha15(-/-)
      Galphaq(-/-) double-knockout mice (which express only Galpha11 in most
      hematopoietic cells), and Galpha11(-/-) mice, suggesting functional redundancy in
      Gq class signaling. Inflammatory challenges, including thioglycolate-induced
      peritonitis and infection with Trichinella spiralis, stimulated similar responses
      in Galpha15(-/-) adults and wild-type siblings. Agonist-stimulated Ca(2+) release
      from intracellular stores was assayed to identify signaling defects in primary
      cultures of thioglycolate-elicited macrophages isolated from Galpha15(-/-) mice. 
      C5a-stimulated phosphoinositide accumulation and Ca(2+) release was significantly
      reduced in Galpha15(-/-) macrophages. Ca(2+) signaling was abolished only in
      mutant cells pretreated with pertussis toxin, suggesting that the C5a receptor
      couples to both Galpha15 and Galphai in vivo. Signaling evoked by other receptors
      coupled by Gq class alpha subunits appeared normal in Galpha15(-/-) macrophages. 
      Despite discrete signaling defects, compensation by coexpressed Gq and/or Gi
      class alpha subunits may suppress abnormalities in Galpha15-deficient mice.
FAU - Davignon, I
AU  - Davignon I
AD  - Pharmacology Department, UT Southwestern, Dallas TX 75235-9041, USA.
FAU - Catalina, M D
AU  - Catalina MD
FAU - Smith, D
AU  - Smith D
FAU - Montgomery, J
AU  - Montgomery J
FAU - Swantek, J
AU  - Swantek J
FAU - Croy, J
AU  - Croy J
FAU - Siegelman, M
AU  - Siegelman M
FAU - Wilkie, T M
AU  - Wilkie TM
LA  - eng
GR  - R01 DK047890/DK/NIDDK NIH HHS/United States
GR  - T32 GM007062/GM/NIGMS NIH HHS/United States
GR  - 5-T32-GM07062/GM/NIGMS NIH HHS/United States
GR  - DK47890/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Thioglycolates)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.1 (G protein alpha 16)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
RN  - EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Fetus
MH  - GTP-Binding Protein alpha Subunits, Gq-G11
MH  - GTP-Binding Proteins/deficiency/genetics/physiology
MH  - Hematopoiesis/*genetics/physiology
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/*physiology
MH  - Heterotrimeric GTP-Binding Proteins/deficiency/genetics/*physiology
MH  - Inflammation/*genetics/physiopathology
MH  - Macrophages, Peritoneal/drug effects/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Peritonitis/physiopathology
MH  - Phosphatidylinositols/metabolism
MH  - Recombination, Genetic
MH  - Restriction Mapping
MH  - Signal Transduction/genetics
MH  - Thioglycolates/toxicity
MH  - Trichinella spiralis
MH  - Trichinellosis/physiopathology
PMC - PMC85196
EDAT- 2000/01/11 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/01/11 09:00
PHST- 2000/01/11 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/01/11 09:00 [entrez]
AID - 10.1128/mcb.20.3.797-804.2000 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2000 Feb;20(3):797-804. doi: 10.1128/mcb.20.3.797-804.2000.