PMID- 10026201
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 9
DP  - 1999 Feb 26
TI  - gp49B1 inhibits IgE-initiated mast cell activation through both immunoreceptor 
      tyrosine-based inhibitory motifs, recruitment of src homology 2 domain-containing 
      phosphatase-1, and suppression of early and late calcium mobilization.
PG  - 5791-6
AB  - We define by molecular, pharmacologic, and physiologic approaches the proximal 
      mechanism by which the immunoglobulin superfamily member gp49B1 inhibits mast 
      cell activation mediated by the high affinity Fc receptor for IgE (FcepsilonRI). 
      In rat basophilic leukemia-2H3 cells expressing transfected mouse gp49B1, 
      mutation of tyrosine to phenylalanine in either of the two immunoreceptor 
      tyrosine-based inhibitory motifs of the gp49B1 cytoplasmic domain partially 
      suppressed gp49B1-mediated inhibition of exocytosis, whereas mutation of both 
      abolished inhibitory capacity. Sodium pervanadate elicited tyrosine 
      phosphorylation of native gp49B1 and association of the tyrosine phosphatases src 
      homology 2 domain-containing phosphatase-1 (SHP-1) and SHP-2 in mouse bone 
      marrow-derived mast cells (mBMMCs). SHP-1 associated transiently with gp49B1 
      within 1 min after coligation of gp49B1 with cross-linked FcepsilonRI in mBMMCs. 
      SHP-1-deficient mBMMCs exhibited a partial loss of gp49B1-mediated inhibition of 
      FcepsilonRI-induced exocytosis at concentrations of IgE providing optimal 
      exocytosis, revealing a central, but not exclusive, SHP-1 requirement in the 
      counter-regulatory pathway. Coligation of gp49B1 with cross-linked FcepsilonRI on 
      mBMMCs inhibited early release of calcium from intracellular stores and 
      subsequent influx of extracellular calcium, consistent with SHP-1 participation. 
      Because exocytosis is complete within 2 min in mBMMCs, our studies establish a 
      role for SHP-1 in the initial counter-regulatory cellular responses whereby 
      gp49B1 immunoreceptor tyrosine-based inhibition motifs rapidly transmit 
      inhibition of FcepsilonRI-mediated exocytosis.
FAU - Lu-Kuo, J M
AU  - Lu-Kuo JM
AD  - Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
FAU - Joyal, D M
AU  - Joyal DM
FAU - Austen, K F
AU  - Austen KF
FAU - Katz, H R
AU  - Katz HR
LA  - eng
GR  - AI-31599/AI/NIAID NIH HHS/United States
GR  - AI-41144/AI/NIAID NIH HHS/United States
GR  - HL-36110/HL/NHLBI 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 Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, Surface)
RN  - 0 (Gp49a protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lilrb4 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, IgE)
RN  - 0 (Receptors, Immunologic)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 42HK56048U (Tyrosine)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Ptpn11 protein, mouse)
RN  - EC 3.1.3.48 (Ptpn11 protein, rat)
RN  - EC 3.1.3.48 (Ptpn6 protein, mouse)
RN  - EC 3.1.3.48 (Ptpn6 protein, rat)
RN  - EC 3.1.3.48 (SH2 Domain-Containing Protein Tyrosine Phosphatases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, Surface/genetics/*physiology
MH  - Binding Sites
MH  - Bone Marrow Cells/immunology
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - Exocytosis
MH  - Immunoglobulin E/*physiology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mast Cells/*immunology
MH  - Membrane Glycoproteins/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Protein Phosphatase 1
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/chemistry/*metabolism
MH  - Receptors, IgE/*antagonists & inhibitors/chemistry
MH  - *Receptors, Immunologic
MH  - SH2 Domain-Containing Protein Tyrosine Phosphatases
MH  - Sequence Homology, Amino Acid
MH  - Tyrosine/*antagonists & inhibitors
MH  - src Homology Domains
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - S0021-9258(19)87724-4 [pii]
AID - 10.1074/jbc.274.9.5791 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Feb 26;274(9):5791-6. doi: 10.1074/jbc.274.9.5791.