A Drosophila protein-tyrosine phosphatase associates with an adapter protein required for axonal guidance

A Drosophila protein-tyrosine phosphatase associates with an adapter protein required for axonal guidance
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DOI:
10.1074/jbc.271.29.17002
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发表时间:
1996-07-19
影响因子:
4.8
通讯作者:
Dixon, JE
Dixon, JE
中科院分区:
生物学2区
文献类型:
--
作者:
Clemens, JC;Ursuliak, Z;Dixon, JE

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我们利用酵母双杂交系统分离了一个新的果蝇衔接蛋白,它与果蝇蛋白酪氨酸磷酸酶(PTP)dPTP 61 F相互作用。果蝇中该蛋白质的缺失导致突变的光感受器轴突表型长发绺(doch)(Garrity,P,A,Rao,Y,Salecker,I.,和Zipursky,S,L,(1996)Cell 85,639-650),Dock类似于哺乳动物癌蛋白Nck,并含有三个Src同源性3(SH 3)结构域和一个Src同源性2(SH 2)结构域。dPTP 61 F与Dock的相互作用通过免疫沉淀实验在体内证实,含有来自PTP的非催化结构域的五个PXXP基序的序列足以与Dock相互作用。这表明与PTP的结合是由Dock的一个或多个SH 3结构域介导的。Dock的免疫沉淀也共沉淀分子量为190和145 kDa的两种酪氨酸磷酸化蛋白。Dock和这些酪氨酸磷酸化蛋白之间的相互作用可能是由Dock SH 2结构域介导的。这些发现确定了Dock的潜在信号转导伙伴,并提出了dPTP 61 F和未鉴定的磷酸化蛋白在轴突导向中的作用。
We have used the yeast two-hybrid system to isolate a novel Drosophila adapter protein, which interacts with the Drosophila protein-tyrosine phosphatase (PTP) dPTP61F. Absence of this protein in Drosophila causes the mutant photoreceptor axon phenotype dreadlocks (doch) (Garrity, P, A, Rao, Y,, Salecker, I., and Zipursky, S, L, (1996) Cell 85, 639-650), Dock is similar to the mammalian oncoprotein Nck and contains three Src homology 3 (SH3) domains and one Src homology 2 (SH2) domain, The interaction of dPTP61F with Dock was confirmed in vivo by immune precipitation experiments, A sequence containing five PXXP motifs from the noncatalytic domain of the PTP is sufficient for interaction with Dock, This suggests that binding to the PTP is mediated by one or more of the SH3 domains of Dock. Immune precipitations of Dock also co precipitate two tyrosine-phosphorylated proteins having molecular masses of 190 and 145 kDa. Interactions between Dock and these tyrosine-phosphorylated proteins are likely mediated by the Dock SH2 domain, These findings identify potential signal-transducing partners of Dock and propose a role for dPTP61F and the unidentified phosphoproteins in axonal guidance.