This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1he8
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Ras activation of phosphoinositide 3-kinase (PI3K) is important for | + | Ras activation of phosphoinositide 3-kinase (PI3K) is important for survival of transformed cells. We find that PI3Kgamma is strongly and directly activated by H-Ras G12V in vivo or by GTPgammaS-loaded H-Ras in vitro. We have determined a crystal structure of a PI3Kgamma/Ras.GMPPNP complex. A critical loop in the Ras binding domain positions Ras so that it uses its switch I and switch II regions to bind PI3Kgamma. Mutagenesis shows that interactions with both regions are essential for binding PI3Kgamma. Ras also forms a direct contact with the PI3Kgamma catalytic domain. These unique Ras/PI3Kgamma interactions are likely to be shared by PI3Kalpha. The complex with Ras shows a change in the PI3K conformation that may represent an allosteric component of Ras activation. |
==Disease== | ==Disease== | ||
| Line 17: | Line 17: | ||
[[Category: Phosphatidylinositol 3-kinase]] | [[Category: Phosphatidylinositol 3-kinase]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Davis, C | + | [[Category: Davis, C T.]] |
| - | [[Category: Eccleston, J | + | [[Category: Eccleston, J F.]] |
| - | [[Category: Hawkins, P | + | [[Category: Hawkins, P T.]] |
[[Category: Lara-Gonzalez, S.]] | [[Category: Lara-Gonzalez, S.]] | ||
| - | [[Category: Pacold, M | + | [[Category: Pacold, M E.]] |
[[Category: Perisic, O.]] | [[Category: Perisic, O.]] | ||
[[Category: Stephens, L.]] | [[Category: Stephens, L.]] | ||
[[Category: Suire, S.]] | [[Category: Suire, S.]] | ||
| - | [[Category: Walker, E | + | [[Category: Walker, E H.]] |
| - | [[Category: Williams, R | + | [[Category: Williams, R L.]] |
[[Category: GNP]] | [[Category: GNP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
| Line 43: | Line 43: | ||
[[Category: second messenger generation]] | [[Category: second messenger generation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:00:21 2008'' |
Revision as of 11:00, 21 February 2008
|
RAS G12V-PI 3-KINASE GAMMA COMPLEX
Contents |
Overview
Ras activation of phosphoinositide 3-kinase (PI3K) is important for survival of transformed cells. We find that PI3Kgamma is strongly and directly activated by H-Ras G12V in vivo or by GTPgammaS-loaded H-Ras in vitro. We have determined a crystal structure of a PI3Kgamma/Ras.GMPPNP complex. A critical loop in the Ras binding domain positions Ras so that it uses its switch I and switch II regions to bind PI3Kgamma. Mutagenesis shows that interactions with both regions are essential for binding PI3Kgamma. Ras also forms a direct contact with the PI3Kgamma catalytic domain. These unique Ras/PI3Kgamma interactions are likely to be shared by PI3Kalpha. The complex with Ras shows a change in the PI3K conformation that may represent an allosteric component of Ras activation.
Disease
Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Thyroid carcinoma, follicular, somatic OMIM:[190020]
About this Structure
1HE8 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Phosphatidylinositol 3-kinase, with EC number 2.7.1.137 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma., Pacold ME, Suire S, Perisic O, Lara-Gonzalez S, Davis CT, Walker EH, Hawkins PT, Stephens L, Eccleston JF, Williams RL, Cell. 2000 Dec 8;103(6):931-43. PMID:11136978
Page seeded by OCA on Thu Feb 21 13:00:21 2008
Categories: Homo sapiens | Phosphatidylinositol 3-kinase | Protein complex | Davis, C T. | Eccleston, J F. | Hawkins, P T. | Lara-Gonzalez, S. | Pacold, M E. | Perisic, O. | Stephens, L. | Suire, S. | Walker, E H. | Williams, R L. | GNP | MG | Gmppnp | Gtp | H-ras g12v | Heat domain | Oncogene protein | Phosphoinositide 3-kinase gamma - h-ras g12v complex | Pi 3-k | Pi 3-kinase | Pi3k | Ras effector | Ras-binding domain | Second messenger generation
