PMID- 10488096
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 39
DP  - 1999 Sep 24
TI  - SHP-1 regulates Lck-induced phosphatidylinositol 3-kinase phosphorylation and
      activity.
PG  - 27583-9
AB  - Ligation of the T cell antigen receptor (TCR) activates the Src family tyrosine
      kinase p56 Lck, which, in turn, phosphorylates a variety of intracellular
      substrates. The phosphatidylinositol 3-kinase (PI3K) and the tyrosine phosphatase
      SHP-1 are two Lck substrates that have been implicated in TCR signaling. In this 
      study, we demonstrate that SHP-1 co-immunoprecipitates with the p85 regulatory
      subunit of PI3K in Jurkat T cells, and that this association is increased by
      ligation of the TCR complex. Co-expression of SHP-1 and PI3K with a
      constitutively activated form of Lck in COS7 cells demonstrated the
      carboxyl-terminal SH2 domain of PI3K to inducibly associate with the full-length 
      SHP-1 protein. By contrast, a truncated SHP-1 mutant lacking the Lck
      phosphorylation site (Tyr(564)) failed to bind p85. Wild-type but not
      catalytically inactive SHP-1 induced dephosphorylation of p85. Furthermore,
      expression of SHP-1 decreased PI3K enzyme activity in anti-phosphotyrosine
      immunoprecipitates and phosphorylation of serine 473 in Akt, a process dependent 
      on PI3K activity. These results indicate the presence of a functional interaction
      between PI3K and SHP-1 and suggest that PI3K signaling, which has been implicated
      in cell proliferation, apoptosis, cytoskeletal reorganization, and many other
      biological activities, can be regulated by SHP-1 in T lymphocytes.
FAU - Cuevas, B
AU  - Cuevas B
AD  - Division of Medicine, and the Cell Growth Regulation Laboratory, University of
      Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
FAU - Lu, Y
AU  - Lu Y
FAU - Watt, S
AU  - Watt S
FAU - Kumar, R
AU  - Kumar R
FAU - Zhang, J
AU  - Zhang J
FAU - Siminovitch, K A
AU  - Siminovitch KA
FAU - Mills, G B
AU  - Mills GB
LA  - eng
GR  - CA71418/CA/NCI 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 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (Lymphocyte Specific Protein Tyrosine Kinase p56(lck))
RN  - EC 3.1.3.48 (PTPN11 protein, human)
RN  - EC 3.1.3.48 (PTPN6 protein, human)
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 (SH2 Domain-Containing Protein Tyrosine Phosphatases)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - COS Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Jurkat Cells
MH  - Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/*metabolism
MH  - Macromolecular Substances
MH  - Mutagenesis, Site-Directed
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/*metabolism
MH  - Receptors, Antigen, T-Cell/*physiology
MH  - Recombinant Proteins/metabolism
MH  - SH2 Domain-Containing Protein Tyrosine Phosphatases
MH  - Sequence Deletion
MH  - Signal Transduction
MH  - Transfection
MH  - Tyrosine
MH  - src Homology Domains
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - 10.1074/jbc.274.39.27583 [doi]
AID - S0021-9258(19)52159-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Sep 24;274(39):27583-9. doi: 10.1074/jbc.274.39.27583.