title: Conformational transitions and interactions underlying the function of membrane embedded receptor protein kinases.
abstract: Among membrane receptors, the single-span receptor protein kinases occupy a broad but specific functional niche determined by distinctive features of the underlying transmembrane signaling mechanisms that are briefly overviewed on the basis of some of the most representative examples, followed by a more detailed discussion of several hierarchical levels of organization and interactions involved. All these levels, including single-molecule interactions (e.g., dimerization, liganding, chemical modifications), local processes (e.g. lipid membrane perturbations, cytoskeletal interactions), and larger scale phenomena (e.g., effects of membrane surface shape or electrochemical potential gradients) appear to be closely integrated to achieve the observed diversity of the receptor functioning. Different species of receptor protein kinases meet their specific functional demands through different structural features defining their responses to stimulation, but certain common patterns exist. Signaling by receptor protein kinases is typically associated with the receptor dimerization and clustering, ligand-induced rearrangements of receptor domains through allosteric conformational transitions with involvement of lipids, release of the sequestered lipids, restriction of receptor diffusion, cytoskeleton and membrane shape remodeling. Understanding of complexity and continuity of the signaling processes can help identifying currently neglected opportunities for influencing the receptor signaling with potential therapeutic implications. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation. Electronic address: bon@nmr.ru.
authors.forename: Eduard V
authors.initials: EV
authors.lastname: Bocharov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation.
authors.forename: Georgy V
authors.initials: GV
authors.lastname: Sharonov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Bocharova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya ul. 16/10, Moscow, 117997, Russian Federation.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Pavlov
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics*; D003599:Cytoskeleton / Q000737:chemistry / Q000235:genetics; D019281:Dimerization; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008563:Membrane Lipids; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases
keywords: cytoskeleton remodeling; lipid raft; protein-lipid and protein-protein interactions; receptor tyrosine kinase; signal transduction; single-span membrane protein