Tyrosine phosphorylation of a 94-kDa protein associated with GRB2/ASH is implicated in the signal transduction of hematopoietic survival factors.
Tyrosine phosphorylation of a 94-kDa protein associated with GRB2/ASH is implicated in the signal transduction of hematopoietic survival factors.
复制标题
与 GRB2/ASH 相关的 94 kDa 蛋白的酪氨酸磷酸化涉及造血存活因子的信号转导。
DOI：
10.1006/bbrc.1996.0744
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发表时间：
1996
影响因子：
3.1
通讯作者：
H. Hirai
中科院分区：
文献类型：
--
作者：
Y. Hanazono;K. Sasaki;H. Odai;Y. Yazaki;H. Hirai
Grb2/Ash是一个含有Src同源(SH)2和3结构域的接头分子。我们已经检测了造血细胞中的Grb2/Ash相关蛋白，并注意到其中一个94 kDa的磷酸酪氨酸蛋白(Pp94)。GST融合蛋白与磷酸酪氨酸类似物苯磷酸的结合实验表明，Grb2/Ash的SH2结构域是pp94与Grb2/Ash结合所必需的。Pp94的酪氨酸磷酸化是快速和短暂的，只有在细胞受到细胞生存所必需的因子(生存因子)刺激时才能观察到。激酶抑制剂星形孢子素和染料木素抑制UT-7细胞的增殖。然而，金雀异黄素并不抑制细胞的存活，而星形孢子素既抑制细胞的增殖又抑制细胞的存活。Pp94酪氨酸磷酸化对星状孢子素敏感，对染料木素耐药。Pp94的酪氨酸磷酸化可能与细胞的存活有关，而与细胞的增殖无关。
Grb2/Ash is an adapter molecule that contains Src-homology (SH) 2 and 3 domains. We have examined Grb2/Ash-associated proteins in hematopoietic cells, and have noted a 94-kDa phosphotyrosine-containing protein (pp94) among them. It was shown that the SH2 domain of Grb2/Ash is necessary for the binding of pp94 to Grb2/Ash from the binding experiments using the GST Fusion proteins and the phosphotyrosine analogue phenylphosphate. Tyrosine phosphorylation of pp94 was rapid and transient, and was only observed when the cells were stimulated with factors that were absolutely required for survival of the cells (survival factors). The kinase inhibitors, staurosporine and genistein, inhibit the proliferation UT-7 cells. However, genistein does not inhibit the survival of the cells while staurosporine inhibits both the proliferation and the survival of the cells. Tyrosine phosphorylation of pp94 was sensitive to staurosporine but resistant to genistein. It is possible that tyrosine phosphorylation of pp94 might be related to the survival rather than to the proliferation of the cells.