Distinct usages of phospholipase Cγ and Shc in intracellular signaling stimulated by neurotrophins

Masashi Yamada, Tadahiro Numakawa, Hisatsugu Koshimizu, Keiko Tanabe, Kazuyo Wada, Shinichi Koizumi, Hiroshi Hatanaka

Research output: Contribution to journalArticle

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Abstract

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 Cγ (PLCγ) and Shc in intracellular signaling stimulated by neurotrophins. BDNF stimulated much stronger interactions of PLCγ 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 PLCγ-dependent increases in intracellular Ca2+ 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 PLCγ and between Trk and Shc. These differences may lead to the distinct biological functions of neurotrophins.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalBrain Research
Volume955
Issue number1-2
DOIs
Publication statusPublished - 15-11-2002

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Nerve Growth Factors
Type C Phospholipases
Brain-Derived Neurotrophic Factor
Neurotrophin 3
Nerve Growth Factor
PC12 Cells
Tyrosine
Neurons
Neuronal Plasticity
Receptor Protein-Tyrosine Kinases
Phosphoric Monoester Hydrolases
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Yamada, Masashi ; Numakawa, Tadahiro ; Koshimizu, Hisatsugu ; Tanabe, Keiko ; Wada, Kazuyo ; Koizumi, Shinichi ; Hatanaka, Hiroshi. / Distinct usages of phospholipase Cγ and Shc in intracellular signaling stimulated by neurotrophins. In: Brain Research. 2002 ; Vol. 955, No. 1-2. pp. 183-190.
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Distinct usages of phospholipase Cγ and Shc in intracellular signaling stimulated by neurotrophins. / Yamada, Masashi; Numakawa, Tadahiro; Koshimizu, Hisatsugu; Tanabe, Keiko; Wada, Kazuyo; Koizumi, Shinichi; Hatanaka, Hiroshi.

In: Brain Research, Vol. 955, No. 1-2, 15.11.2002, p. 183-190.

Research output: Contribution to journalArticle

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T1 - Distinct usages of phospholipase Cγ and Shc in intracellular signaling stimulated by neurotrophins

AU - Yamada, Masashi

AU - Numakawa, Tadahiro

AU - Koshimizu, Hisatsugu

AU - Tanabe, Keiko

AU - Wada, Kazuyo

AU - Koizumi, Shinichi

AU - Hatanaka, Hiroshi

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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 Cγ (PLCγ) and Shc in intracellular signaling stimulated by neurotrophins. BDNF stimulated much stronger interactions of PLCγ 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 PLCγ-dependent increases in intracellular Ca2+ 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 PLCγ and between Trk and Shc. These differences may lead to the distinct biological functions of neurotrophins.

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