Hydrophobic modifications of Ras proteins by isoprenoid groups and fatty acids--More than just membrane anchoring.
During the last years, post-translational modification of peripheral membrane proteins with hydrophobic side groups has been attributed to a couple of additional functions than just simple anchoring into lipid bilayers. In particular isoprenylation and N- and S-acylation did quicken interest in terms of specific recognition elements for protein-protein interactions and as hydrophobic switches that allow for temporal regulated association with distinct target structures. Furthermore new insights into the heterogeneity of natural membranes have connected the physical properties of e.g. farnesyl or palmitoyl side chains with a preference for such sub-compartments as lipid rafts or caveolae. In this review the impact of the two frequently realized modifications by isoprenylation and S-acylation on the process of cellular signal transduction is exemplified with proteins of the Ras and Rab family of small GTP-binding proteins.
Pechlivanis
Markos
M
Department of Structural Biology, Max Planck Institute for Molecular Physiology, D-44227 Dortmund, Germany.
Kuhlmann
Juergen
J
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000502:physiology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D047668:Inteins / Q000502:physiology; D008074:Lipoproteins / Q000138:chemical synthesis; D021962:Membrane Microdomains / Q000502:physiology*; D008958:Models, Molecular; D025941:Protein Interaction Mapping; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013729:Terpenes / Q000378:metabolism*; D014166:Transferases; D018631:ras Proteins / Q000737:chemistry / Q000378:metabolism*; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D005227:Fatty Acids; D020730:Guanine Nucleotide Dissociation Inhibitors; D008074:Lipoproteins; C095279:Rab geranylgeranyl transferase beta-subunit; D013729:Terpenes; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D018631:ras Proteins