PMID- 10482988
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20190915
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 13
IP  - 9
DP  - 1999 Sep
TI  - SHC and SHIP phosphorylation and interaction in response to activation of the
      FLT3 receptor.
PG  - 1374-82
AB  - The FLT3 receptor tyrosine kinase and its ligand, FL, regulate the development of
      hematopoietic stem cells and early B lymphoid progenitors. FL has a strong
      capacity to boost production of dendritic and natural killer cells in vivo,
      thereby providing a new and promising tool for anti-cancer immunotherapy.
      Intracellular FLT3 signaling involves tyrosine phosphorylation of several
      cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC
      phosphorylation occurs at tyrosine 239/240 and 313. SHC possesses two
      phosphotyrosine-binding domains: an amino-terminal phosphotyrosine binding (PTB) 
      and a carboxy-terminal Src Homology 2 (SH2) domain. Neither is required for SHC
      phosphorylation, but the PTB domain is necessary and sufficient for SHC binding
      to the SH2 containing inositol phosphatase (SHIP). Overexpression of SHC
      increases the level of SHIP phosphorylation on tyrosines in response to FLT3
      activation, suggesting that SHC availability is a limiting step for SHIP
      phosphorylation. This effect is observed only if the SHC PTB domain is
      functional. Interestingly, SHC overexpression in FLT3-activatable Ba/F3 cells
      limits FLT3-dependent cell growth and this effect requires tyrosine 313. Taken
      together, the present data show that SHC can antagonize cell proliferation
      induced by FLT3 stimulation and regulate phosphorylation of the SHIP negative
      regulator. In addition, our study provides the structural bases for SHC
      phosphorylation and formation of the SHC/SHIP complex.
FAU - Marchetto, S
AU  - Marchetto S
AD  - Laboratoire d'Oncologie Moleculaire, INSERM U119, Marseille, France.
FAU - Fournier, E
AU  - Fournier E
FAU - Beslu, N
AU  - Beslu N
FAU - Aurran-Schleinitz, T
AU  - Aurran-Schleinitz T
FAU - Dubreuil, P
AU  - Dubreuil P
FAU - Borg, J P
AU  - Borg JP
FAU - Birnbaum, D
AU  - Birnbaum D
FAU - Rosnet, O
AU  - Rosnet O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Proteins)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
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  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Animals
MH  - Cell Line
MH  - Enzyme Activation
MH  - Genes, myc
MH  - Genetic Code
MH  - Kinetics
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
MH  - Phosphoric Monoester Hydrolases/*metabolism
MH  - Phosphorylation
MH  - Proteins/*metabolism
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Retroviridae/genetics
MH  - Shc Signaling Adaptor Proteins
MH  - *src Homology Domains
EDAT- 1999/09/14 00:00
MHDA- 1999/09/14 00:01
CRDT- 1999/09/14 00:00
PHST- 1999/09/14 00:00 [pubmed]
PHST- 1999/09/14 00:01 [medline]
PHST- 1999/09/14 00:00 [entrez]
AID - 10.1038/sj.leu.2401527 [doi]
PST - ppublish
SO  - Leukemia. 1999 Sep;13(9):1374-82. doi: 10.1038/sj.leu.2401527.