Protooncogenes-Signaling in Development and Neoplasia

所有的细胞都必须与它们的环境交流。 他们通过识别与细胞受体相互作用的细胞外信号分子来实现这一点，从而引发有意义的细胞内反应。受体酪氨酸激酶的跨膜信号形成了这一合作计划的概念基础。该计划中的各个实验室组件相互作用，以解决跨膜信号转导的基本问题。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通过膜传递结构变化，将配体结合的能量传递到有意义的细胞内事件？下游信号成分如何识别受体胞内区的变化，从而改变单个细胞或细胞群体的生长、分化和迁移，最后，这一信号过程中的扰动如何导致恶性表型？各个部件实验室从不同的方向处理这些概念上相关的问题。斯蒂芬·戈夫继续研究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道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·杰塞尔和理查德·阿克塞尔的实验室研究神经系统中的信号分子，这些分子定义神经身份并决定轴突靶向的精确度，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.