title: Chaperone-mediated specificity in Ras and Rap signaling.
abstract: Ras and Rap proteins are closely related small guanosine triphosphatase (GTPases) that share similar effector-binding domains but operate in a very different signaling networks; Ras has a dominant role in cell proliferation, while Rap mediates cell adhesion. Ras and Rap proteins are regulated by several shared processes such as post-translational modification, phosphorylation, activation by guanine exchange factors and inhibition by GTPase-activating proteins. Sub-cellular localization and trafficking of these proteins to and from the plasma membrane are additional important regulatory features that impact small GTPases function. Despite its importance, the trafficking mechanisms of Ras and Rap proteins are not completely understood. Chaperone proteins play a critical role in trafficking of GTPases and will be the focus of the discussion in this work. We will review several aspects of chaperone biology focusing on specificity toward particular members of the small GTPase family. Understanding this specificity should provide key insights into drug development targeting individual small GTPases.
authors.affiliation: a Division of Rheumatology, Department of Medicine and.
authors.forename: Inbar
authors.initials: I
authors.lastname: Azoulay-Alfaguter
authors.forename: Marianne
authors.initials: M
authors.lastname: Strazza
authors.forename: Adam
authors.initials: A
authors.lastname: Mor
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D020668:rap GTP-Binding Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D018832:Molecular Chaperones; D020668:rap GTP-Binding Proteins; D018631:ras Proteins
keywords: 14-3-3; PDE6δ; Rap1; Ras; RhoGDI; SmgGDS; chaperones