PMID- 10092678
OWN - NLM
STAT- MEDLINE
DCOM- 19990427
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 14
DP  - 1999 Apr 2
TI  - The signaling adapter FRS-2 competes with Shc for binding to the nerve growth
      factor receptor TrkA. A model for discriminating proliferation and
      differentiation.
PG  - 9861-70
AB  - We have isolated a human cDNA for the signaling adapter molecule
      FRS-2/suc1-associated neurotrophic factor target and shown that it is
      tyrosine-phosphorylated in response to nerve growth factor (NGF) stimulation.
      Importantly, we demonstrate that the phosphotyrosine binding domain of FRS-2
      directly binds the Trk receptors at the same phosphotyrosine residue that binds
      the signaling adapter Shc, suggesting a model in which competitive binding
      between FRS-2 and Shc regulates differentiation versus proliferation. Consistent 
      with this model, FRS-2 binds Grb-2, Crk, the SH2 domain containing tyrosine
      phosphatase SH-PTP-2, the cyclin-dependent kinase substrate p13(suc1), and the
      Src homology 3 (SH3) domain of Src, providing a functional link between TrkA,
      cell cycle, and multiple NGF signaling effectors. Importantly, overexpression of 
      FRS-2 in cells expressing an NGF nonresponsive TrkA receptor mutant reconstitutes
      the ability of NGF to stop cell cycle progression and to stimulate neuronal
      differentiation.
FAU - Meakin, S O
AU  - Meakin SO
AD  - Neurodegeneration Research Group, The John P. Robarts Research Institute, London,
      Ontario N6A 5K8, Canada. smeakin@rri.on.ca
FAU - MacDonald, J I
AU  - MacDonald JI
FAU - Gryz, E A
AU  - Gryz EA
FAU - Kubu, C J
AU  - Kubu CJ
FAU - Verdi, J M
AU  - Verdi JM
LA  - eng
SI  - GENBANK/AF036717
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 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (FRS2 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (SHC1 protein, human)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - 0 (Shc1 protein, mouse)
RN  - 0 (Src Homology 2 Domain-Containing, Transforming Protein 1)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding, Competitive
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cell Line
MH  - Humans
MH  - *Membrane Proteins
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nerve Growth Factors/metabolism
MH  - Phosphoproteins/*metabolism
MH  - Protein Binding
MH  - Proteins/*metabolism
MH  - Receptor, trkA/*metabolism
MH  - Sequence Alignment
MH  - Shc Signaling Adaptor Proteins
MH  - Src Homology 2 Domain-Containing, Transforming Protein 1
MH  - Tyrosine/metabolism
MH  - *src Homology Domains
EDAT- 1999/03/27 00:00
MHDA- 1999/03/27 00:01
CRDT- 1999/03/27 00:00
PHST- 1999/03/27 00:00 [pubmed]
PHST- 1999/03/27 00:01 [medline]
PHST- 1999/03/27 00:00 [entrez]
AID - 10.1074/jbc.274.14.9861 [doi]
AID - S0021-9258(19)87327-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 2;274(14):9861-70. doi: 10.1074/jbc.274.14.9861.