Structure of the MRAS-SHOC2-PP1C phosphatase complex.

ABSTRACT: RAS-MAPK signalling is fundamental for cell proliferation and is altered in most human cancers^1-3. However, our mechanistic understanding of how RAS signals through RAF is still incomplete. Although studies revealed snapshots for autoinhibited and active RAF-MEK1-14-3-3 complexes⁴, the intermediate steps that lead to RAF activation remain unclear. The MRAS-SHOC2-PP1C holophosphatase dephosphorylates RAF at serine 259, resulting in the partial displacement of 14-3-3 and RAF-RAS association^3,5,6. MRAS, SHOC2 and PP1C are mutated in rasopathies-developmental syndromes caused by aberrant MAPK pathway activation^6-14-and SHOC2 itself has emerged as potential target in receptor tyrosine kinase (RTK)-RAS-driven tumours^15-18. Despite its import

SUBMITTER: Hauseman ZJ 

PROVIDER: S-EPMC9452295 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature