TY - JOUR
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
N1 - Funding Information:
We thank Regeneron Pharmaceutical Co. for the kind gifts of BDNF and NT-3. This work was supported in part by a Grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.
PY - 2002/11/15
Y1 - 2002/11/15
N2 - 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.
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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U2 - 10.1016/S0006-8993(02)03432-7
DO - 10.1016/S0006-8993(02)03432-7
M3 - Article
C2 - 12419535
AN - SCOPUS:0037111115
VL - 955
SP - 183
EP - 190
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -