A soluble version of the receptor-like protein tyrosine phosphatase κ stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade
A soluble version of the receptor-like protein tyrosine phosphatase κ stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade
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DOI：
10.1006/mcne.1999.0758
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发表时间：
1999-06-01
影响因子：
3.5
通讯作者：
Doherty, P
中科院分区：
文献类型：
--
作者：
Drosopoulos, NE;Walsh, FS;Doherty, P
受体样蛋白酪氨酸磷酸酶kappa(RPTP Kappa)在神经系统中以一种与轴突生长和引导相一致的方式表达。RPTP kappa的胞外区具有与细胞黏附分子相同的结构特征，能够支持亲和性黏附。在本研究中，我们制备了一种含有RPTP kappa全胞外区的可溶性Fc嵌合蛋白。亲和力捕获后，RPTP kappa-Fc被证明促进了Covesphere珠子的聚集，证实了其亲和性结合活性。当RPTP kappa嵌合体作为一种可溶性分子加入到小脑神经元培养中时，它能刺激轴突生长。GRB2的细胞通透性多肽抑制剂和PD 098059可显著抑制轴突生长反应，PD 500已被用于抑制多种细胞类型的MEK1的激活。这些结果表明，RPTP kappa可以刺激轴突生长，并提供了证据，表明这可能涉及Grb2与MAPK信号转导通路的偶联。
Receptor-like protein tyrosine phosphatase kappa (RPTP kappa) is expressed in the nervous system in a manner consistent with a role in axonal growth and guidance. The extracellular domain of RPTP kappa shares structural features with cell adhesion molecules and can support homophilic adhesion. In the present study we produced a soluble Fc-chimeric protein containing the full extracellular domain of RPTP kappa. Following affinity capture, the RPTP kappa-Fc was shown to promote the aggregation of Covasphere beads, confirming its homophilic binding activity. When added to cultures of cerebellar neurons as a soluble molecule, the RPTP kappa chimera stimulated neurite outgrowth. The neurite outgrowth response was substantially inhibited by a cell-permeable peptide inhibitor of Grb2 and by PD 098059, a drug that has been used to inhibit MEK1 activation in a wide range of cell types. These results demonstrate that RPTP kappa can stimulate neurite outgrowth and provide evidence that this might involve the coupling of Grb2 to a MAPK signal transduction cascade.