Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation.
Cancer Metastasis Rev
; 39(4): 1067-1073, 2020 12.
Article
in En
| MEDLINE
| ID: mdl-32936431
ABSTRACT
Somatic mutations in the RAS genes are frequent in human tumors, especially in pancreatic, colorectal, and non-small-cell lung cancers. Such mutations generally decrease the ability of Ras to hydrolyze GTP, maintaining the protein in a constitutively active GTP-bound form that drives uncontrolled cell proliferation. Efforts to develop drugs that target Ras oncoproteins have been unsuccessful. Recent emerging data suggest that Ras regulation is more complex than the scientific community has believed for decades. In this review, we summarize advances in the "textbook" view of Ras activation. We also discuss a novel type of Ras regulation that involves direct phosphorylation and dephosphorylation of Ras tyrosine residues. The discovery that pharmacological inhibition of the tyrosine phosphoprotein phosphatase SHP2 maintains mutant Ras in an inactive state suggests that SHP2 could be a novel drug target for the treatment of Ras-driven human cancers.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Tyrosine
/
Proto-Oncogene Proteins p21(ras)
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Metastasis Rev
Journal subject:
NEOPLASIAS
Year:
2020
Type:
Article
Affiliation country:
Hungary