Activation of cellular p21ras by myristoylation.
Biochem Soc Trans
; 17(5): 867-9, 1989 Oct.
Article
en En
| MEDLINE
| ID: mdl-2695362
p21ras is palmitoylated on a cysteine residue near the C-terminus. Changing Cys-186 to Ser in oncogenic forms produces a non-palmitoylated protein that fails to associate with membranes and does not transform NIH 3T3 cells. To examine whether palmitate acts in a general way to increase ras protein hydrophobicity, or is involved in more specific interactions between p21ras and membranes, we constructed genes that encode non-palmitoylated ras proteins containing myristic acid at their N-termini. Myristoylated, activated ras, without palmitate (61Leu/186Ser) exhibited both efficient membrane association and full transforming activity. Unexpectedly, we found that myristoylated forms of normal cellular ras were also potently transforming. Myristoylated c-ras retained the high GTP binding and GTPase characteristic of the cellular protein and, moreover, bound predominantly GDP in vivo. This implied that it continued to interact with GAP (GTPase-activating protein). While the membrane binding induced by myristate permitted transformation, only palmitate produced a normal (non-transforming) association of ras with membranes and must therefore regulate ras function by some unique property that myristate does not mimic. Myristoylation thus represents a novel mechanism by which the ras proto-oncogene protein can become transforming.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína Oncogénica p21(ras)
/
Membrana Celular
/
Miristatos
/
Ácidos Mirísticos
Límite:
Animals
Idioma:
En
Revista:
Biochem Soc Trans
Año:
1989
Tipo del documento:
Article
Pais de publicación:
Reino Unido