PMID- 10196222
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 16
DP  - 1999 Apr 16
TI  - Brain-derived neurotrophic factor induces phosphorylation of fibroblast growth 
      factor receptor substrate 2.
PG  - 11321-7
AB  - Brain-derived neurotrophic factor (BDNF) promotes neuronal survival. Gaining an 
      understanding of how BDNF, via the tropomyosin-related kinase B (TRKB) receptor, 
      elicits specific cellular responses is of contemporary interest. Expression of 
      mutant TrkB in fibroblasts, where tyrosine 484 was changed to phenylalanine, 
      abrogated Shc association with TrkB, but only attenuated and did not block 
      BDNF-induced phosphorylation of mitogen-activated protein kinase (MAPK). This 
      suggests there is another BDNF-induced signaling mechanism for activating MAPK, 
      which compelled a search for other TrkB substrates. BDNF induces phosphorylation 
      of fibroblast growth factor receptor substrate 2 (FRS2) in both fibroblasts 
      engineered to express TrkB and human neuroblastoma (NB) cells that naturally 
      express TrkB. Additionally, BDNF induces phosphorylation of FRS2 in primary 
      cultures of cortical neurons, thus showing that FRS2 is a physiologically 
      relevant substrate of TrkB. Data are presented demonstrating that BDNF induces 
      association of FRS2 with growth factor receptor-binding protein 2 (GRB2) in 
      cortical neurons, fibroblasts, and NB cells, which in turn could activate the 
      RAS/MAPK pathway. This is not dependent on Shc, since BDNF does not induce 
      association of Shc and FRS2. Finally, the experiments suggest that FRS2 and 
      suc-associated neurotrophic factor-induced tyrosine-phosphorylated target are the 
      same protein.
FAU - Easton, J B
AU  - Easton JB
AD  - Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 
      Memphis, Tennessee 38105-2794, USA.
FAU - Moody, N M
AU  - Moody NM
FAU - Zhu, X
AU  - Zhu X
FAU - Middlemas, D S
AU  - Middlemas DS
LA  - eng
GR  - 1 R29 CA 71628/CA/NCI NIH HHS/United States
GR  - CA 21765/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (FRS2 protein, human)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (GRB2 protein, human)
RN  - 0 (Grb2 protein, rat)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Receptor, Ciliary Neurotrophic Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 42HK56048U (Tyrosine)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Line
MH  - GRB2 Adaptor Protein
MH  - Humans
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Phenylalanine/genetics/metabolism
MH  - Phosphoproteins/genetics/*metabolism
MH  - Phosphorylation
MH  - Proteins/metabolism
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/genetics
MH  - Receptor, Ciliary Neurotrophic Factor
MH  - Receptors, Nerve Growth Factor/genetics
MH  - Tyrosine/genetics/metabolism
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - S0021-9258(19)73641-2 [pii]
AID - 10.1074/jbc.274.16.11321 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 16;274(16):11321-7. doi: 10.1074/jbc.274.16.11321.