کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1951393 | 1537962 | 2007 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction](/preview/png/1951393.png)
Rit is a novel member of the Ras superfamily of small GTP-binding proteins that regulates signaling pathways controlling cellular fate determination. Constitutively activated mutants of Rit induce terminal differentiation of pheochromocytoma (PC6) cells resulting in a sympathetic neuron-like phenotype characterized by the development of highly-branched neurites. Rit signaling has been found to activate several downstream pathways including MEK/ERK, p38 MAPK, Ral-specific guanine nucleotide exchange factors (GEFs), and Rit associates with the Par6 cell polarity machinery. In this study, a series of Rit effector loop mutants was generated to test the importance of these cellular targets to Rit-mediated neuronal differentiation. We find that Rit-mediated neuritogenesis is dependent upon MEK/ERK MAP kinase signaling but independent of RalGEF activation. In addition, in vivo binding studies identified a novel mechanism of Par6 interaction, suggesting that the cell polarity machinery may serve to spatially restrict Rit signaling.
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1773, Issue 12, December 2007, Pages 1793–1800