PMID- 10570274
OWN - NLM
STAT- MEDLINE
DCOM- 19991220
LR  - 20161124
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 11
DP  - 1999 Dec 1
TI  - Tyrosine phosphorylation of shc in response to B cell antigen receptor engagement
      depends on the SHIP inositol phosphatase.
PG  - 5891-5
AB  - Tyrosine phosphorylation of Shc in response to B cell Ag receptor (BCR)
      engagement creates binding sites for the Src homology 2 (SH2) domain of Grb2.
      This facilitates the recruitment of both Grb2. Sos complexes and Grb2. SHIP
      complexes to the plasma membrane where Sos can activate Ras and SH2
      domain-containing inositol phosphatase (SHIP) can dephosphorylate
      phosphatidylinositol 3,4,5-trisphosphate. Given the importance of Shc
      phosphorylation, we investigated the mechanism by which the BCR stimulates this
      response. We found that both the SH2 domain and phosphotyrosine-binding (PTB)
      domain of Shc are important for BCR-induced tyrosine phosphorylation of Shc and
      the subsequent binding of Grb2 to Shc. The unexpected finding that the PTB domain
      of Shc is required for Shc phosphorylation was investigated further. Because the 
      major ligand for the Shc PTB domain is SHIP, we asked whether the interaction of 
      Shc with SHIP was required for BCR-induced tyrosine phosphorylation of Shc. Using
      SHIP-deficient DT40 cells, we show that SHIP is necessary for the BCR to induce
      significant levels of Shc tyrosine phosphorylation. BCR-induced tyrosine
      phosphorylation of Shc could be restored in the these cells by expressing
      wild-type SHIP but not by expressing a mutant form of SHIP that cannot bind to
      Shc. This suggests that BCR-induced tyrosine phosphorylation of Shc may depend on
      the binding of SHIP to the Shc PTB domain. Thus, we have described a novel role
      for SHIP in BCR signaling, promoting the tyrosine phosphorylation of Shc.
FAU - Ingham, R J
AU  - Ingham RJ
AD  - Department of Microbiology and Immunology, University of British Columbia,
      Vancouver, British Columbia, Canada.
FAU - Okada, H
AU  - Okada H
FAU - Dang-Lawson, M
AU  - Dang-Lawson M
FAU - Dinglasan, J
AU  - Dinglasan J
FAU - van Der Geer, P
AU  - van Der Geer P
FAU - Kurosaki, T
AU  - Kurosaki T
FAU - Gold, M R
AU  - Gold MR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (GRB2 protein, human)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 0 (SHC1 protein, human)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - 0 (Src Homology 2 Domain-Containing, Transforming Protein 1)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.86 (INPPL1 protein, human)
RN  - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases)
SB  - AIM
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - B-Lymphocytes/*immunology
MH  - Binding Sites
MH  - GRB2 Adaptor Protein
MH  - Humans
MH  - Mutation
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
MH  - Phosphoric Monoester Hydrolases/*metabolism
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Protein Binding
MH  - Proteins/genetics/*metabolism
MH  - Receptors, Antigen, B-Cell/*metabolism
MH  - Shc Signaling Adaptor Proteins
MH  - Src Homology 2 Domain-Containing, Transforming Protein 1
MH  - Tyrosine/*metabolism
MH  - src Homology Domains
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - ji_v163n11p5891 [pii]
PST - ppublish
SO  - J Immunol. 1999 Dec 1;163(11):5891-5.