ACTIVATION MECHANISMS OF THE SKY PROTEIN TYROSINE KINASE

描述：（改编自申请人摘要）T和B淋巴细胞 在正常的免疫反应中起着关键作用。 然而， 这些细胞的激活导致多种自身免疫性疾病， 癌的 外源抗原对T细胞和B细胞的激活是由 T和B细胞抗原受体，并涉及一个级联反应， 生物化学事件最终导致宿主对外来生物的反应， 病原体 蛋白酪氨酸激酶（PTK）在T-和 B细胞活化，并参与这一级联反应的启动事件。 本提案中提出的实验将剖析Syk PTK是如何 参与T细胞和B细胞的功能。 该PTK对于 B细胞的发育和功能，也可能在功能中发挥作用。 的T细胞。 了解Syk PTK在B细胞中的功能将有助于 提供了更多的淋巴细胞信号转导机制的知识 以及对PTK调控机制的更深入了解。 另外这些 研究可以提供额外的机制信息， 为癌症药物设计中更合理的治疗干预奠定基础， 自身免疫性疾病和移植排斥反应。

DESCRIPTION: (Adapted from the applicant's abstract) T and B lymphocytes play critical roles in the normal immune response. However, aberrant activation of these cells result in a variety of autoimmune disorders and cancers. Activation of T- and B-cells by foreign antigens are mediated by T- and B-cell antigen receptors, respectively, and involves a cascade of biochemical events the culminate in a host response against foreign pathogens. Protein tyrosine kinases (PTKs) play an integral role in T- and B-cell activation and are involved in the initiating events in this cascade. The experiments proposed in this proposal will dissect how the Syk PTK is involved in both T-and B-cell function. This PTK is critical for the development and function of B cells and may also have a role in the function of T cells. An understanding of how the Syk PTK functions in B-cells will provide a greater knowledge of signal transduction mechanisms in lymphocytes and greater insight into regulatory mechanisms of PTKs. In addition, these studies may provide additional mechanistic information that may serve as the basis for more rational therapeutic interventions in drug design for cancer, autoimmune diseases and transplantation rejection.