PMID- 10428862
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 32
DP  - 1999 Aug 6
TI  - Independent SH2-binding sites mediate interaction of Dok-related protein with
      RasGTPase-activating protein and Nck.
PG  - 22775-84
AB  - A murine embryonic cDNA library was screened for potential substrates of the Src 
      family kinase, Lyn, using a phosphorylation-screening strategy. One cDNA that we 
      identified encodes Dok-related protein (DokR), a protein with homology to
      p62(dok) (Dok), and members of the insulin receptor substrate-1 family of
      proteins. Analysis of murine tissue extracts with DokR-specific antisera revealed
      that DokR protein is expressed at highest levels in lymphoid tissues.
      Co-expression of a FLAG epitope-tagged form of DokR (FLAG-DokR) with Lyn in
      embryonic kidney 293T cells resulted in constitutive phosphorylation of FLAG-DokR
      on tyrosine residues and consequential physical association with
      RasGTPase-activating protein (GAP) and the Nck adaptor protein. Stimulation of
      BaF/3 hematopoietic cells co-expressing the epidermal growth factor (EGF)
      receptor tyrosine kinase and FLAG-DokR with EGF also induced phosphorylation of
      FLAG-DokR and promoted its association with GAP. Immunoprecipitation experiments 
      using DokR-specific antibodies revealed an interaction between endogenous DokR
      and a 150-kDa protein that is tyrosine-phosphorylated in EGF-stimulated BaF/3
      cells. The molecular basis of the interactions involving DokR with GAP and Nck
      was investigated using a novel glutathione S-transferase fusion protein binding
      assay and/or site-directed mutagenesis. Tandem SH2-binding sites containing
      Tyr-276 and Tyr-304 were shown to mediate binding of DokR to GAP, whereas Tyr-351
      mediated the binding of DokR to Nck. These results suggest that DokR participates
      in numerous signaling pathways.
FAU - Lock, P
AU  - Lock P
AD  - Ludwig Institute for Cancer Research and the Cooperative Research Center for
      Cellular Growth Factors, P. O. Box 2008, Royal Melbourne Hospital, Parkville
      3050, Australia. Peter.Lock@Ludwig.edu.au
FAU - Casagranda, F
AU  - Casagranda F
FAU - Dunn, A R
AU  - Dunn AR
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (Dok2 protein, mouse)
RN  - 0 (FRS2 protein, human)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Irs2 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nck protein)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Carrier Proteins/*metabolism
MH  - Cell Lineage
MH  - DNA, Complementary/genetics
MH  - GTPase-Activating Proteins
MH  - Gene Library
MH  - Hematopoietic Stem Cells
MH  - Insulin Receptor Substrate Proteins
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lymphoid Tissue
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oncogene Proteins/*metabolism
MH  - Phosphoproteins/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Proteins/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Substrate Specificity
MH  - Tissue Distribution
MH  - *src Homology Domains
MH  - src-Family Kinases/*metabolism
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - 10.1074/jbc.274.32.22775 [doi]
AID - S0021-9258(18)81605-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 6;274(32):22775-84. doi: 10.1074/jbc.274.32.22775.