PMID- 10508618
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20191210
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 9
IP  - 18
DP  - 1999 Sep 23
TI  - Recruitment of Dok-R to the EGF receptor through its PTB domain is required for
      attenuation of Erk MAP kinase activation.
PG  - 1057-60
AB  - Dok (for downstream of tyrosine kinases) proteins are a newly identified family
      of docking molecules that are characterized by the presence of an amino-terminal 
      pleckstrin homology (PH) domain, a central putative phosphotyrosine-binding (PTB)
      domain and numerous potential sites of tyrosine phosphorylation [1] [2] [3] [4]
      [5] [6]. Here, we explore the potential role of the Dok family member Dok-R (also
      known as p56(Dok2) or FRIP) in signaling pathways mediated by the epidermal
      growth factor (EGF) receptor. An intact PTB domain in Dok-R was critical for its 
      association with two PTB-binding consensus sites on the EGF receptor and the PH
      domain further contributed to stable in vivo binding and tyrosine phosphorylation
      of Dok-R. Multiple sites on Dok-R were tyrosine-phosphorylated following EGF
      stimulation; phosphorylated Tyr276 and Tyr304 are proposed to dock the tandem Src
      homology 2 (SH2) domains of the p21(Ras) GTPase-activating protein rasGAP and
      Tyr351 mediates an association with the SH2 domain of the adapter protein Nck.
      Interestingly, we have found that Dok-R could attenuate EGF-stimulated
      mitogen-activated protein (MAP) kinase activation independently of its
      association with rasGAP. Together, these results suggest that Dok-R has an
      important role downstream of growth factor receptors as a potential negative
      regulator of signal transduction.
FAU - Jones, N
AU  - Jones N
AD  - Division of Cancer Biology Research Sunnybrook and Women's College Health
      Sciences Centre Department of Medical Biophysics University of Toronto Toronto,
      Ontario, Canada.
FAU - Dumont, D J
AU  - Dumont DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Carrier Proteins)
RN  - 0 (DOK2 protein, human)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Nck protein)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Carrier Proteins/chemistry/*metabolism
MH  - Chlorocebus aethiops
MH  - Enzyme Activation
MH  - ErbB Receptors/*metabolism
MH  - GRB2 Adaptor Protein
MH  - MAP Kinase Signaling System/*physiology
MH  - Molecular Sequence Data
MH  - Oncogene Proteins/metabolism
MH  - Phosphoproteins/chemistry/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - *Protein Processing, Post-Translational
MH  - Protein Structure, Tertiary
MH  - Proteins/metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Shc Signaling Adaptor Proteins
MH  - Transfection
MH  - src Homology Domains
EDAT- 1999/10/06 09:00
MHDA- 2000/02/19 09:00
CRDT- 1999/10/06 09:00
PHST- 1999/10/06 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 1999/10/06 09:00 [entrez]
AID - S0960-9822(99)80458-8 [pii]
AID - 10.1016/s0960-9822(99)80458-8 [doi]
PST - ppublish
SO  - Curr Biol. 1999 Sep 23;9(18):1057-60. doi: 10.1016/s0960-9822(99)80458-8.