PMID- 2824610
OWN - NLM
STAT- MEDLINE
DCOM- 19880112
LR  - 20131121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 139
IP  - 11
DP  - 1987 Dec 1
TI  - Involvement of a guanine-nucleotide-binding component in membrane IgM-stimulated 
      phosphoinositide breakdown.
PG  - 3604-13
AB  - Cross-linking of membrane immunoglobulin, the B cell receptor for antigen, 
      activates the phosphoinositide signal transduction pathway. The initial event in 
      this pathway is the hydrolysis of phosphatidylinositol 4,5-bisphosphate 
      (PtdInsP2) by phospholipase C. This reaction yields two intracellular second 
      messengers, diacylglycerol, which activates protein kinase C, and inositol 
      trisphosphate, which causes an increase in cytoplasmic Ca2+. The experiments 
      reported here demonstrate that activation of phospholipase C by membrane IgM 
      (mIgM) involves a guanine nucleotide-dependent step. Saponin was used to 
      permeabilize WEHI-231 B lymphoma cells and permit direct manipulation of 
      nucleotide and Ca2+ concentrations. Very high levels of Ca2+ (greater than 100 
      microM) activated the phospholipase maximally without a requirement for 
      cross-linking of mIgM. However, at much lower, physiologically relevant Ca2+ 
      concentrations (100 to 500 nM), receptor-stimulated PtdInsP2 hydrolysis could be 
      demonstrated. The ability of anti-IgM antibodies to activate phospholipase C in 
      permeabilized WEHI-231 cells was greatly increased by nonhydrolyzable guanosine 
      5'-triphosphate (GTP) analogues (guanosine-5'-O-(3-thiotriphosphate) or 
      5'-guanylylimidodiphosphate), but not by guanosine diphosphate or guanosine 
      diphosphate analogues or by a nonhydrolyzable analogue of adenosine triphosphate. 
      This specificity for GTP analogues is consistent with the hypothesis that a 
      GTP-binding regulatory protein analogous to those that couple receptors to 
      adenylate cyclase is involved in the activation of phospholipase C by mIgM in 
      WEHI-231 B lymphoma cells. In order to characterize this putative GTP-binding 
      component, we examined the ability of pertussis toxin and cholera toxin to affect 
      anti-IgM-stimulated inositol phosphate production. These bacterial toxins 
      covalently modify and modulate the activity of various GTP-binding regulatory 
      proteins and in some cell types can block receptor-stimulated PtdInsP2 breakdown. 
      In WEHI-231 B lymphoma cells, neither toxin blocked signaling by mIgM. Thus mIgM 
      appears to be coupled to the phosphoinositide signaling pathway by a 
      GTP-dependent component that is insensitive to both pertussis toxin and cholera 
      toxin.
FAU - Gold, M R
AU  - Gold MR
AD  - Department of Microbiology and Immunology, University of California, San 
      Francisco 94143.
FAU - Jakway, J P
AU  - Jakway JP
FAU - DeFranco, A L
AU  - DeFranco AL
LA  - eng
GR  - AI-20038/AI/NIAID 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  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adenylate Cyclase Toxin)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 0 (Thionucleotides)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 9012-63-9 (Cholera Toxin)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenylate Cyclase Toxin
MH  - Animals
MH  - B-Lymphocytes/drug effects/immunology/*physiology
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cholera Toxin/pharmacology
MH  - GTP-Binding Proteins/*physiology
MH  - Guanosine 5'-O-(3-Thiotriphosphate)
MH  - Guanosine Triphosphate/analogs & derivatives/metabolism
MH  - Immunoglobulin M/*immunology
MH  - Mice
MH  - Pertussis Toxin
MH  - Phosphatidylinositols/*metabolism
MH  - Receptors, Antigen, B-Cell/*immunology
MH  - Thionucleotides/metabolism
MH  - Tumor Cells, Cultured/drug effects/immunology/physiology
MH  - Virulence Factors, Bordetella/pharmacology
EDAT- 1987/12/01 00:00
MHDA- 1987/12/01 00:01
CRDT- 1987/12/01 00:00
PHST- 1987/12/01 00:00 [pubmed]
PHST- 1987/12/01 00:01 [medline]
PHST- 1987/12/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1987 Dec 1;139(11):3604-13.