Kinetic Mechanism of Formation of Hyperactive Embryonic Ras in Cells

Biochemistry
Michael WeyJongyun Heo

Abstract

Embryonic Ras (ERas)-a new subset of Ras proteins-are characterized by a unique p-loop residue, unique Switch II residues, and an unusual extended N-terminus. When expressed, both murine and human ERas are highly populated in their GTP-bound forms. The expression of murine ERas is linked to the development of murine embryonic cells, and the expression of human ERas is correlated to certain human cancers. Mutation-based kinetic analyses, in combination with assessments of the kinetic parameter-based calculation of the fraction of the GTP-bound active form of ERas proteins, explain the kinetic mechanism that produces the unprecedented hyperactive ERas. The ERas-specific p-loop residue contributes ERas proteins to intrinsically populate their GTP-bound form in cells. Furthermore, the ERas-specific Switch II residues block the catalytic action of p120GAP on ERas proteins. This blockage sustains the previously mentioned GTP-bound ERas proteins. In essence, the combined work of the ERas-specific p-loop and Switch II residues populates the exceedingly high GTP-bound form of ERas in cells. This study also rules out any kinetic function of the unique ERas-specific N-terminus in the production of the hyperactive GTP-bound ERas in cells. ...Continue Reading

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Citations

Aug 6, 2020·The Journal of Biological Chemistry·Hope Gloria UmutesiJongyun Heo
Apr 16, 2019·Small GTPases·Hanh My HoangJongyun Heo
Jul 23, 2021·The Journal of Biological Chemistry·Hanh My HoangJongyun Heo

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