Analysis of signal transduction mechanism in lipid rafts

我们已经证明，神经节苷脂GD3（R24）的抗体免疫沉淀src家族酪氨酸激酶林恩从原代小脑颗粒细胞和R24处理的完整细胞诱导林恩激活和快速酪氨酸磷酸化的几个底物，这表明神经节苷脂GD3与林恩的功能协会。在这项研究中，R24处理的原代小脑颗粒细胞增强桩蛋白在酪氨酸残基118磷酸化，并诱导丝状肌动蛋白组装和神经突生长。小脑生长锥膜组分的R24处理诱导68kDa蛋白的显著酪氨酸磷酸化，该蛋白与酪氨酸残基118处的磷酸氨苄共迁移。已知桩蛋白的酪氨酸磷酸化调节细胞形态中的肌动蛋白细胞色素依赖性变化。神经节苷脂GD3的信号转导通过桩蛋白的酪氨酸磷酸化参与生长锥形态。

We have demonstrated that antibody to ganglioside GD3 (R24) immunoprecipitates src-family tyrosine kinase Lyn from primary cerebellar granule cells and R24 treatment of the intact cells induces Lyn activation and rapid tyrosine phosphorylation of several substrates, suggesting the functional association of ganglioside GD3 with Lyn. In this study, R24 treatment of primary cerebellar granule cells enhances phosphorylation of paxillin at tyrosine residue 118 and induces filamentous actin assembly and neurite outgrowth. R24 treatment of cerebellar growth cone membrane fraction induces prominent tyrosine phosphorylation of 68kDa protein which comigrates with phosphopaxillin at tyrosine residue 118. Tyrosine phosphorylation of paxillin is known to regulate actin cytoskeleton-dependent changes in cell morphology. Signal transduction by ganglioside GD3 is involved in growth cone morphology via tyrosine phosphorylation of paxillin.