PMID- 12419535
OWN - NLM
STAT- MEDLINE
DCOM- 20030131
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 955
IP  - 1-2
DP  - 2002 Nov 15
TI  - Distinct usages of phospholipase C gamma and Shc in intracellular signaling 
      stimulated by neurotrophins.
PG  - 183-90
AB  - Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and 
      neurotrophin-3 (NT-3), members of the neurotrophin family, bind to and activate 
      TrkA, TrkB and TrkC, respectively, members of the Trk receptor tyrosine kinase 
      family, to exert various effects including promotion of differentiation and 
      survival, and regulation of synaptic plasticity in neuronal cells. Many reports 
      have suggested that different neurotrophins show distinct biological functions, 
      although molecular mechanisms by which neurotrophins exert their different 
      functions remain unclear. In the present study, we found distinct usages of 
      phospholipase Cgamma (PLCgamma) and Shc in intracellular signaling stimulated by 
      neurotrophins. BDNF stimulated much stronger interactions of PLCgamma with Trk 
      than NGF and NT-3 in PC12 cells stably expressing TrkB and cultured cerebral 
      cortical neurons, respectively, although BDNF, NGF and NT-3 induced similar 
      levels of tyrosine phosphorylation of Trk. Furthermore, the cultured cortical 
      neurons showed large PLCgamma-dependent increases in intracellular Ca(2+) levels 
      in response to BDNF compared with NT-3. In Shc signaling, NGF, but not BDNF, 
      displayed interactions between Trk and Shc in a phenylarsine oxide (PAO; an 
      inhibitor of tyrosine phosphatase)-dependent manner in TrkB-expressing PC12 
      cells. These results indicated that neurotrophins stimulate distinct kinds of 
      interactions between Trk and PLCgamma and between Trk and Shc. These differences 
      may lead to the distinct biological functions of neurotrophins.
FAU - Yamada, Masashi
AU  - Yamada M
AD  - Division of Protein Biosynthesis, Institute for Protein Research, Osaka 
      University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan. 
      yamada@protein.osaka-u.ac.jp
FAU - Numakawa, Tadahiro
AU  - Numakawa T
FAU - Koshimizu, Hisatsugu
AU  - Koshimizu H
FAU - Tanabe, Keiko
AU  - Tanabe K
FAU - Wada, Kazuyo
AU  - Wada K
FAU - Koizumi, Shinichi
AU  - Koizumi S
FAU - Hatanaka, Hiroshi
AU  - Hatanaka H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Isoenzymes)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Proteins)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - 0 (Shc1 protein, rat)
RN  - 0 (Src Homology 2 Domain-Containing, Transforming Protein 1)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Animals
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/enzymology/physiology
MH  - Embryo, Mammalian
MH  - Female
MH  - Intracellular Fluid/drug effects/enzymology/physiology
MH  - Isoenzymes/*physiology
MH  - Male
MH  - Nerve Growth Factors/*pharmacology/physiology
MH  - Neurons/drug effects/physiology
MH  - PC12 Cells
MH  - Phospholipase C gamma
MH  - Proteins/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/biosynthesis/genetics
MH  - Shc Signaling Adaptor Proteins
MH  - Signal Transduction/*drug effects/physiology
MH  - Src Homology 2 Domain-Containing, Transforming Protein 1
MH  - Type C Phospholipases/*physiology
EDAT- 2002/11/07 04:00
MHDA- 2003/02/01 04:00
CRDT- 2002/11/07 04:00
PHST- 2002/11/07 04:00 [pubmed]
PHST- 2003/02/01 04:00 [medline]
PHST- 2002/11/07 04:00 [entrez]
AID - S0006899302034327 [pii]
AID - 10.1016/s0006-8993(02)03432-7 [doi]
PST - ppublish
SO  - Brain Res. 2002 Nov 15;955(1-2):183-90. doi: 10.1016/s0006-8993(02)03432-7.