Sattler M, Durstin M A, Frank D A, Okuda K, Kaushansky K, Salgia R, Griffin J D
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Exp Hematol. 1995 Aug;23(9):1040-8.
Thrombopoietin (TPO) is a growth and differentiation factor for megakaryocyte-lineage cells. The receptor for TPO, c-MPL, is a member of the hematopoietic cytokine receptor family and has previously been shown to rapidly activate one or more cytoplasmic tyrosine kinases after ligand binding. In this study, we found that activation of the TPO receptor rapidly induced tyrosine phosphorylation of two members of the Jak tyrosine kinase family, JAK2 and TYK2, but not JAK1 or JAK3, in two different factor-dependent hematopoietic cell lines. The activation of both JAK2 and TYK2 was dose- and time-dependent and was associated with rapid tyrosine phosphorylation of a series of STAT proteins including STAT1, STAT3, and STAT5. Gel-shift assays indicated that one or more of these STATs is likely to participate in the formation of specific DNA-binding complexes. The activation of tyrosine kinases and signal propagation through tyrosine phosphorylation are likely to represent important initial steps in mediating the activities of TPO in myeloid cells.
血小板生成素（TPO）是巨核细胞系细胞的生长和分化因子。TPO的受体c-MPL是造血细胞因子受体家族的成员，先前已表明其在配体结合后能迅速激活一种或多种细胞质酪氨酸激酶。在本研究中，我们发现TPO受体的激活在两种不同的因子依赖性造血细胞系中迅速诱导了Jak酪氨酸激酶家族的两个成员JAK2和TYK2的酪氨酸磷酸化，但未诱导JAK1或JAK3的酪氨酸磷酸化。JAK2和TYK2的激活均呈剂量和时间依赖性，并且与包括STAT1、STAT3和STAT5在内的一系列STAT蛋白的快速酪氨酸磷酸化相关。凝胶迁移分析表明，这些STAT中的一种或多种可能参与特异性DNA结合复合物的形成。酪氨酸激酶的激活以及通过酪氨酸磷酸化的信号传导可能是介导TPO在髓系细胞中活性的重要初始步骤。
