PMID- 10521483
OWN - NLM
STAT- MEDLINE
DCOM- 19991123
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 43
DP  - 1999 Oct 22
TI  - Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking
      site mediates cell survival and migration.
PG  - 30896-905
AB  - The Tek/Tie2 receptor tyrosine kinase plays a pivotal role in vascular and
      hematopoietic development. To study the signal transduction pathways that are
      mediated by this receptor, we have used the yeast two-hybrid system to identify
      signaling molecules that associate with the phosphorylated Tek receptor. Using
      this approach, we demonstrate that five molecules, Grb2, Grb7, Grb14, Shp2, and
      the p85 subunit of phosphatidylinositol 3-kinase can interact with Tek in a
      phosphotyrosine-dependent manner through their SH2 domains. Mapping of the
      binding sites of these molecules on Tek reveals the presence of a multisubstrate 
      docking site in the carboxyl tail of Tek (Tyr(1100)). Mutation of this site
      abrogates binding of Grb2 and Grb7 to Tek in vivo, and this site is required for 
      tyrosine phosphorylation of Grb7 and p85 in vivo. Furthermore, stimulation of
      Tek-expressing cells with Angiopoietin-1 results in phosphorylation of both Tek
      and p85 and in activation of endothelial cell migration and survival pathways
      that are dependent in part on phosphatidylinositol 3-kinase. Taken together,
      these results demonstrate that Angiopoietin-1-induced signaling from the Tek
      receptor is mediated by a multifunctional docking site that is responsible for
      activation of both cell migration and cell survival pathways.
FAU - Jones, N
AU  - Jones N
AD  - Division of Cancer Biology Research, Sunnybrook and Women's College Health
      Sciences Centre, University of Toronto, Toronto, Ontario M4N 3M5.
FAU - Master, Z
AU  - Master Z
FAU - Jones, J
AU  - Jones J
FAU - Bouchard, D
AU  - Bouchard D
FAU - Gunji, Y
AU  - Gunji Y
FAU - Sasaki, H
AU  - Sasaki H
FAU - Daly, R
AU  - Daly R
FAU - Alitalo, K
AU  - Alitalo K
FAU - Dumont, D J
AU  - Dumont DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Grb14 protein, mouse)
RN  - 0 (Grb2 protein, mouse)
RN  - 0 (Grb7 protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 149058-53-7 (GRB7 Adaptor Protein)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, TIE-2)
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 (Ptpn6 protein, mouse)
RN  - EC 3.1.3.48 (SH2 Domain-Containing Protein Tyrosine Phosphatases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Cell Movement/physiology
MH  - Cell Survival/physiology
MH  - Embryo, Mammalian
MH  - ErbB Receptors/*metabolism
MH  - GRB2 Adaptor Protein
MH  - GRB7 Adaptor Protein
MH  - Gene Library
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lung/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Myocardium/metabolism
MH  - Phosphatidylinositol 3-Kinases/chemistry/metabolism
MH  - Protein Binding
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/metabolism
MH  - Proteins/metabolism
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptor, TIE-2
MH  - Recombinant Fusion Proteins/metabolism
MH  - SH2 Domain-Containing Protein Tyrosine Phosphatases
MH  - Saccharomyces cerevisiae/genetics/growth & development
MH  - src Homology Domains
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1074/jbc.274.43.30896 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 22;274(43):30896-905. doi: 10.1074/jbc.274.43.30896.