Protooncogenes-Signaling in Development and Neoplasia

所有细胞都必须与其环境进行通信。 他们通过识别与细胞受体相互作用的细胞外信号分子来引发有意义的细胞内反应。受体酪氨酸激酶的跨膜信号传导构成了该合作项目的概念基础。 该计划中的各个实验室组成部分相互作用，以解决跨膜信号传导的基本问题。 细胞外信号分子的性质是什么？ 这些分子与特定表面受体的结合如何跨膜传递结构变化，将配体结合的能量转变成有意义的细胞内事件？ 下游信号成分识别受体细胞内结构域的变化如何改变单个细胞或细胞群的生长、分化和迁移，最后，该信号传导过程的扰动如何导致恶性表型？ 各个组成实验室从不同的方向处理这些概念上相关的问题。 Stephen Goff 继续研究 Abelson 酪氨酸激酶在正常发育过程中的功能以及 Abl 激活形式的转化活性。 Frank Costantini 的工作重点是了解 RET 受体酪氨酸激酶在肠神经系统发育中的功能以及导致多种人类癌症的 RET 突变的性质。 汤姆·杰塞尔（Tom Jessell）和理查德·阿克塞尔（Richard Axel）的实验室通过分子研究神经系统中的信号传导，这些分子定义了神经身份并决定了轴突靶向的精确度，但在其他细胞环境中是原癌基因。

All cells must communicate with their environment. They do so by recognizing extracellular signaling molecules that interact with cellular receptors to elicit a meaningful intracellular response. Transmembrane signaling by the receptor tyrosine kinases form the conceptual basis for this collaborative program. The individual laboratory components within this program interact to address basic issues in transmembrane signaling. What are the nature of the extracellular signaling molecules? How does the association of these molecules with specific surface receptors transmit a structural change across the membrane transducing the energy of ligand binding into meaningful intracellular events? How are the changes in intracellular domains of the receptor recognized by downstream signaling components to alter the growth, differentiation and migration of individual cells or cell populations and finally, how do perturbations in this signaling process result in the malignant phenotype? These conceptually related questions are approached from different directions by the individual component laboratories. Stephen Goff continues to examine the function of the Abelson tyrosine kinase during normal development as well as the transforming activity of activating forms of Abl. Frank Costantini's efforts have focused on an understanding of the function of the RET receptor tyrosine kinase in the development of the enteric nervous system and the nature of the mutations in RET that lead to a variety of human cancers. Tom Jessell's and Richard Axel's laboratories study signaling in the nervous system by molecules that define neural identity and dictate the precision of axon targeting, but in other cellular contexts are protooncogenes.