MOLECULAR MECHANISMS OF HEMATOPOIESIS AND LEUKEMIA

了解激酶和磷酸盐之间的动态相互作用是控制介导血细胞发育的细胞质信号传导的关键生化机制。许多从细胞表面受体-配体相互作用传递到细胞核的信息是通过磷酸化蛋白传递的。我们希望了解造血干细胞/祖细胞承诺和分化的分子基础和信号转导途径。我们打算通过研究酪氨酸蛋白磷酸酶Shp-2在造血中的作用来解决这个问题。我们将确定Shp-2在介导造血细胞和内皮细胞共同前体发育中的作用。我们还将确定ras-Erk激酶通路在介导Shp-2控制造血中的重要性。我们的最终目标是，这些研究的发现将允许开发改进的、毒性更低的人类白血病治疗方法。

DESCRIPTION Understanding the dynamic interaction between kinases and phosphates is a critical biochemical mechanism in the control of cytoplasmic signaling that mediates blood cell development. Much of the information passed from cell surface receptor-ligand interaction to the nucleus is transmitted via phosphorylated proteins. We wish to understand the molecular basis and signal transduction pathways responsible for the commitment and differentiation of hematopoietic stem/progenitor cells. We intend to address this question by investigating the role of Shp-2, a protein tyrosine phosphatase, in hematopoiesis. We will determine the role of Shp-2 in mediating the development of a common precursor for hematopoietic and endothelial cells. We will also determine the significance of the ras-Erk kinase pathway in mediating Shp-2 control of hematopoiesis Our ultimate goal is that the findings from these studies will allow for the development of improved and less toxic therapies for human leukemias.