| First Author | Stowe IB | Year | 2012 |
| Journal | Genes Dev | Volume | 26 |
| Issue | 13 | Pages | 1421-6 |
| PubMed ID | 22751498 | Mgi Jnum | J:185345 |
| Mgi Id | MGI:5428340 | Doi | 10.1101/gad.190876.112 |
| Citation | Stowe IB, et al. (2012) A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. Genes Dev 26(13):1421-6 |
| abstractText | The Ras/mitogen-activated protein kinase (MAPK) pathway plays a critical role in transducing mitogenic signals from receptor tyrosine kinases. Loss-of-function mutations in one feedback regulator of Ras/MAPK signaling, SPRED1 (Sprouty-related protein with an EVH1 domain), cause Legius syndrome, an autosomal dominant human disorder that resembles Neurofibromatosis-1 (NF1). Spred1 functions as a negative regulator of the Ras/MAPK pathway; however, the underlying molecular mechanism is poorly understood. Here we show that neurofibromin, the NF1 gene product, is a Spred1-interacting protein that is necessary for Spred1's inhibitory function. We show that Spred1 binding induces the plasma membrane localization of NF1, which subsequently down-regulates Ras-GTP levels. This novel mechanism for the regulation of neurofibromin provides a molecular bridge for understanding the overlapping pathophysiology of NF1 and Legius syndrome. |
