Obermeier A, Bradshaw R A, Seedorf K, Choidas A, Schlessinger J, Ullrich A
Department of Molecular Biology, Max-Planck-Institut für Biochemie, Martinsried, Germany.
EMBO J. 1994 Apr 1;13(7):1585-90. doi: 10.1002/j.1460-2075.1994.tb06421.x.
Differentiation and survival of neuronal cell types requires the action of neurotrophic polypeptides such as nerve growth factor (NGF). In the central and peripheral nervous system and the phaeochromocytoma cell model PC12, NGF exerts its effects through the activation of the signalling capacity of Trk, a receptor tyrosine kinase (RTK) which upon interaction with NGF becomes phosphorylated on tyrosines and thereby acquires the potential to interact with signal-transducing proteins such as phospholipase C-gamma (PLC gamma), phosphatidylinositol-3'-kinase (PI3'-K) and SHC. Mutagenesis of the specific binding sites for these src homology 2 (SH2) domain-containing substrates within the Trk cytoplasmic domain suggests a non-essential function of PI3'-K and reveals a major role for the signal controlled by the SHC binding site at tyrosine 490 and a co-operative function of the PLC gamma-mediated pathway for neuronal differentiation of PC12 cells.
神经元细胞类型的分化和存活需要神经营养多肽的作用，如神经生长因子（NGF）。在中枢和外周神经系统以及嗜铬细胞瘤细胞模型PC12中，NGF通过激活Trk的信号传导能力发挥其作用，Trk是一种受体酪氨酸激酶（RTK），与NGF相互作用后，酪氨酸会发生磷酸化，从而获得与信号转导蛋白（如磷脂酶C-γ（PLCγ）、磷脂酰肌醇-3'-激酶（PI3'-K）和SHC）相互作用的潜力。Trk细胞质结构域内这些含src同源2（SH2）结构域的底物的特异性结合位点的诱变表明PI3'-K的功能并非必需，并揭示了酪氨酸490处SHC结合位点所控制的信号在PC12细胞神经元分化中的主要作用以及PLCγ介导的途径的协同功能。
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