PMID- 8394019
OWN - NLM
STAT- MEDLINE
DCOM- 19930907
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 90
IP  - 15
DP  - 1993 Aug 1
TI  - Src-homology 3 domain of protein kinase p59fyn mediates binding to 
      phosphatidylinositol 3-kinase in T cells.
PG  - 7366-70
AB  - The Src-related tyrosine kinase p59fyn(T) plays an important role in the 
      generation of intracellular signals from the T-cell antigen receptor TCR zeta/CD3 
      complex. A key question concerns the nature and the binding sites of downstream 
      components that interact with this Src-related kinase. p59fyn(T) contains 
      Src-homology 2 and 3 domains (SH2 and SH3) with a capacity to bind to 
      intracellular proteins. One potential downstream target is phosphatidylinositol 
      3-kinase (PI 3-kinase). In this study, we demonstrate that anti-CD3 and anti-Fyn 
      immunoprecipitates possess PI 3-kinase activity as assessed by TLC and HPLC. Both 
      free and receptor-bound p59fyn(T) were found to bind to the lipid kinase. 
      Further, our results indicate that Src-related kinases have developed a novel 
      mechanism to interact with PI 3-kinase. Precipitation using GST fusion proteins 
      containing Fyn SH2, SH3, and SH2/SH3 domains revealed that PI 3-kinase bound 
      principally to the SH3 domain of Fyn. Fyn SH3 bound directly to the p85 subunit 
      of PI 3-kinase as expressed in a baculoviral system. Anti-CD3 crosslinking 
      induced an increase in the detection of Fyn SH3-associated PI 3-kinase activity. 
      Thus PI 3-kinase is a target of SH3 domains and is likely to play a major role in 
      the signals derived from the TCR zeta/CD3-p59fyn complex.
FAU - Prasad, K V
AU  - Prasad KV
AD  - Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
FAU - Janssen, O
AU  - Janssen O
FAU - Kapeller, R
AU  - Kapeller R
FAU - Raab, M
AU  - Raab M
FAU - Cantley, L C
AU  - Cantley LC
FAU - Rudd, C E
AU  - Rudd CE
LA  - eng
GR  - R01 GM041890/GM/NIGMS NIH HHS/United States
GR  - CA51887-02/CA/NCI NIH HHS/United States
GR  - GM36624/GM/NIGMS NIH HHS/United States
GR  - GM41890/GM/NIGMS 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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (CD3 Complex)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (FYN protein, human)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Baculoviridae/genetics
MH  - Binding Sites
MH  - CD3 Complex/metabolism
MH  - Cloning, Molecular
MH  - Humans
MH  - In Vitro Techniques
MH  - Molecular Sequence Data
MH  - Moths
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphotransferases/*metabolism
MH  - Protein Binding
MH  - Proto-Oncogene Proteins/chemistry/*metabolism
MH  - Proto-Oncogene Proteins c-fyn
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes/*metabolism
PMC - PMC47138
EDAT- 1993/08/01 00:00
MHDA- 1993/08/01 00:01
PMCR- 1994/02/01
CRDT- 1993/08/01 00:00
PHST- 1993/08/01 00:00 [pubmed]
PHST- 1993/08/01 00:01 [medline]
PHST- 1993/08/01 00:00 [entrez]
PHST- 1994/02/01 00:00 [pmc-release]
AID - 10.1073/pnas.90.15.7366 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7366-70. doi: 
      10.1073/pnas.90.15.7366.