DOI: 10.1002/prot.340060313. Ras interaction with the GTPase‐activating protein (GAP)

Ras interaction with the GTPase‐activating protein (GAP)

10.1002/prot.340060313

Crossref journal-article

Wiley

Proteins: Structure, Function, and Bioinformatics (311)

Abstract

AbstractBiologically active forms of Ras complexed to GTP can bind to the GTP ase‐activating protein (GAP), which has been implicated as a possible target of Ras in mammalian cells. In order to study the structural features of Ras required for this interaction, we have evaluated a series of mutant ras proteins for the ability to bind GAP and a series of Ras peptides for the ability to interfere with this interaction. Point mutations in the putative effector region of Ras (residues 32–40) that inhibit biological activity also impair Ras binding to GAP. An apparent exception is the Thr to Ser substitution at residue 35; [Ser‐35]Ras binds to GAP as effectively as wild‐type Ras even though this mutant is biologically weak in both mammalian and S. cerevisiae cells. In vitro, [Ser‐35]Ras can also efficiently stimulate the S. cerevisiae target of Ras adenylyl cyclase, indicating that other factors may influence Ras/protein interactions in vivo. Peptides having Ras residues 17–44 and 17–32 competed with the binding of RAS to E. coli‐expressed GAP with IC50 values of 2.4 and 0.9 μM, respectively, whereas Ras peptide 17–26 was without effect up to 400 μM. A related peptide from the yeast GTP‐binding protein YPT1 analogous to Ras peptide 17–32 competed with an IC50 value of 19 μM even though the YPT1 protein itself is unable to bind to GAP. These results suggest that determinants within Ras peptide 17–32 may be important for Ras binding to GAP.

Bibliography

Schaber, M. D., Garsky, V. M., Boylan, D., Hill, W. S., Scolnick, E. M., Marshall, M. S., Sigal, I. S., & Gibbs, J. B. (1989). Ras interaction with the GTPaseâactivating protein (GAP). Proteins: Structure, Function, and Bioinformatics, 6(3), 306â315. Portico.

Authors 8

Michael D. Schaber (first)
Victor M. Garsky (additional)
Douglas Boylan (additional)
Wendy S. Hill (additional)
Edward M. Scolnick (additional)
Mark S. Marshall (additional)
Irving S. Sigal (additional)
Jackson B. Gibbs (additional)

References 36 Referenced 63

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Dates

Type	When
Created	20 years, 2 months ago (May 28, 2005, 9:05 p.m.)
Deposited	1 year, 10 months ago (Oct. 22, 2023, 7:41 a.m.)
Indexed	1 month, 1 week ago (July 11, 2025, 6:11 a.m.)
Issued	36 years, 7 months ago (Jan. 1, 1989)
Published	36 years, 7 months ago (Jan. 1, 1989)
Published Online	21 years, 6 months ago (Feb. 3, 2004)
Published Print	36 years, 7 months ago (Jan. 1, 1989)

Funders 0

None

BibTeX

@article{Schaber_1989, title={Ras interaction with the GTPase‐activating protein (GAP)}, volume={6}, ISSN={1097-0134}, url={http://dx.doi.org/10.1002/prot.340060313}, DOI={10.1002/prot.340060313}, number={3}, journal={Proteins: Structure, Function, and Bioinformatics}, publisher={Wiley}, author={Schaber, Michael D. and Garsky, Victor M. and Boylan, Douglas and Hill, Wendy S. and Scolnick, Edward M. and Marshall, Mark S. and Sigal, Irving S. and Gibbs, Jackson B.}, year={1989}, month=jan, pages={306–315} }

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