Modulation of Ras Signaling by NF1 and CRKL in Development

摘要

Mutations in the NF1 gene are the genetic basis of neurofibromatosis type I, a common genetic disorder which predisposes the patient to neoplasia in the peripheral nervous system as well as other tissues. The NF1 gene encodes a protein called neurofibromin that negatively regulates the small G-protein Ras. Abnormal activation of Ras can cause sustained cell survival and growth in some cells. Ras and other small C-proteins like it are believed to relay critical messages from the cell's environment to the cell nucleus where this information is processed. Crkl (Crk-like) encodes an adapter protein that has been implicated in bridging such messages to small C-proteins like Ras. We have proposed to study the biological role of Crkl during development in conjunction with NF1 and to determine the role of Crkl in regulation of Ras signaling.