PMID- 9851703
OWN - NLM
STAT- MEDLINE
DCOM- 19981228
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 258
IP  - 1
DP  - 1998 Nov 15
TI  - Stimulation of Ca2+-dependent exocytosis and arachidonic acid release in cultured 
      mast cells (RBL-2H3) by a GTPase-deficient mutant of G alpha i3.
PG  - 144-9
AB  - Gi3, a member of the Gi family of heterotrimeric GTP-binding proteins, regulates 
      vesicle trafficking along both the constitutive and regulated pathways. In mast 
      cells, specialized secretory cells which secrete a variety of inflammatory 
      mediators by regulated exocytosis, activation of Gi3 provides a sufficient signal 
      for exocytosis [Aridor, M., Rajmilevich, G., Beaven, M. A. & Sagi-Eisenberg, R. 
      (1993) Science 262, 1569-1572]. Such activation can be achieved in patch-clamped 
      or streptolysin-O (SLO)-permeabilized mast cells by a combination of Ca2+ and 
      nonhydrolyzable analogs of GTP. In contrast, Ca2+-activated exocytosis in intact 
      cells is Gi3 independent. We show here that overexpression of a GTPase-deficient 
      mutant (G alpha i3Q204L), but not of the wild-type form of G alpha i3, in rat 
      basophilic leukemia cells (RBL-2H3), a tumor analog of mucosal mast cells, 
      resulted in marked potentiation of exocytosis and release of arachidonic acid in 
      intact cells activated by a Ca2+ ionophore alone or in combination with the 
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate. In contrast, exocytosis and 
      arachidonic acid release stimulated by aggregation of the cell surface receptors 
      for immunoglobulin E (IgE) were unaffected. These results strongly suggest that 
      the intracellular receptor, responsible for the activation of Gi3, is a 
      low-affinity Ca2+-binding protein that can only be activated during Ca2+ 
      ionophore stimulation. Moreover, these results also suggest that the propagation 
      of the Ca2+-activated and Gi3-mediated signaling pathway requires the blocking of 
      Gi3 GTPase activity. Finally, our results indicate that release of arachidonic 
      acid is at least one of the downstream effectors of Gi3.
FAU - Zussman, A
AU  - Zussman A
AD  - Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv 
      University, Israel.
FAU - Hermuet, S
AU  - Hermuet S
FAU - Sagi-Eisenberg, R
AU  - Sagi-Eisenberg R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Arachidonic Acid/*metabolism
MH  - Calcium/*metabolism
MH  - Cell Line
MH  - *Exocytosis
MH  - GTP Phosphohydrolases/*genetics/metabolism
MH  - GTP-Binding Proteins/*genetics
MH  - Mast Cells/*metabolism
MH  - Transfection
EDAT- 1998/12/16 00:00
MHDA- 1998/12/16 00:01
CRDT- 1998/12/16 00:00
PHST- 1998/12/16 00:00 [pubmed]
PHST- 1998/12/16 00:01 [medline]
PHST- 1998/12/16 00:00 [entrez]
AID - 10.1046/j.1432-1327.1998.2580144.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1998 Nov 15;258(1):144-9. doi: 10.1046/j.1432-1327.1998.2580144.x.