Ran Wei

Date of Award


Degree Type


Degree Name

Master of Science




Dr. Shawn Li


Originally identified as a cell fate determinant, Numb has been found to also act as an epithelial polarity protein, an adaptor, an endocytotic regulator and a tumor suppressor. Recently, anaplastic lymphoma kinase (ALK) was identified as a potential Numb-interacting protein in our lab. ALK is a receptor tyrosine kinase and is expressed mainly within the neonatal brain. Thus ALK likely plays an important role in development of the nervous system. In addition, mutated ALK is associated with a number of cancer cell lines and tumors. In this thesis, the interaction of Numb with ALK was confirmed and was found to involve the Numb-PTB domain. Two Numb putative binding motifs NMAF (1477-1480) and NYGY (1583-1586) were identified on ALK. The Numb-ALK interaction was enhanced upon ALK activation and attenuated upon ALK inhibition. Further investigations suggested that Numb regulated ALK protein expression levels, its cleavage, nuclear localization and downstream Erk signaling.



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