N-terminally myristoylated Ras proteins require palmitoylation or a polybasic domain for plasma membrane localization
Autor: | H. Paterson, John F. Hancock, K. A. Cadwallader, S. G. Macdonald |
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Rok vydání: | 1994 |
Předmět: |
Signal peptide
Molecular Sequence Data Restriction Mapping Palmitic Acid Palmitic Acids Biology Transfection Myristic Acid Polymerase Chain Reaction Cell Line Proto-Oncogene Proteins p21(ras) Cell membrane Palmitoylation Prenylation Mutant protein Chlorocebus aethiops Serine medicine Animals Point Mutation Amino Acid Sequence Cysteine Protein kinase A Molecular Biology DNA Primers Myristoylation Mitogen-Activated Protein Kinase Kinases Base Sequence Sequence Homology Amino Acid Cell Membrane Cell Biology Recombinant Proteins Cell biology medicine.anatomical_structure Biochemistry Protein Biosynthesis Calcium-Calmodulin-Dependent Protein Kinases Mutagenesis Site-Directed lipids (amino acids peptides and proteins) Myristic Acids Protein Kinases Protein Processing Post-Translational Research Article |
Zdroj: | Molecular and Cellular Biology. 14:4722-4730 |
ISSN: | 1098-5549 0270-7306 |
DOI: | 10.1128/mcb.14.7.4722 |
Popis: | Plasma membrane targeting of Ras requires CAAX motif modifications together with a second signal from an adjacent polybasic domain or nearby cysteine palmitoylation sites. N-terminal myristoylation is known to restore membrane binding to H-ras C186S (C-186 is changed to S), a mutant protein in which all CAAX processing is abolished. We show here that myristoylated H-ras C186S is a substrate for palmitoyltransferase, despite the absence of C-terminal farnesylation, and that palmitoylation is absolutely required for plasma membrane targeting of myristoylated H-ras. Similarly, the polybasic domain is required for specific plasma membrane targeting of myristoylated K-ras. In contrast, the combination of myristoylation plus farnesylation results in the mislocalization of Ras to numerous intracellular membranes. Ras that is only myristoylated does not bind with a high affinity to any membrane. The specific targeting of Ras to the plasma membrane is therefore critically dependent on signals that are contained in the hypervariable domain but can be supported by N-terminal myristoylation or C-terminal prenylation. Interestingly, oncogenic Ras G12V that is localized correctly to the plasma membrane leads to mitogen-activated protein kinase activation irrespective of the combination of targeting signals used for localization, whereas Ras G12V that is mislocalized to the cytosol or to other membranes activates mitogen-activated protein kinase only if the Ras protein is farnesylated. |
Databáze: | OpenAIRE |
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