Conformational transitions and interactions underlying the function of membrane embedded receptor protein kinases

• Published in: Biochimica et biophysica acta. Biomembranes Vol. 1859; no. 9; pp. 1417 - 1429
• Main Authors: Bocharov, Eduard V., Sharonov, Georgy V., Bocharova, Olga V., Pavlov, Konstantin V.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2017
• Subjects: Cell Membrane - chemistry; Cell Membrane - genetics; Cytoskeleton - chemistry; Cytoskeleton - genetics; cytoskeleton remodeling; Dimerization; lipid raft; Membrane Lipids - chemistry; Membrane Lipids - metabolism; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Protein Conformation; protein-lipid and protein-protein interactions; Receptor Protein-Tyrosine Kinases - chemistry; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; receptor tyrosine kinase; Signal Transduction; single-span membrane protein; JM; PS; Lo; cytoskeleton remodeling; signal transduction; ECD; single-span membrane protein; RTK; TMD; ICD; GPI-AP; PA; lipid raft; TKL; IDP; protein-lipid and protein-protein interactions; PIP; Ld; receptor tyrosine kinase; SH2
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2017.01.025

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. [Display omitted] •The structural traits of single-span receptors define their specific functional niche•Diverse levels of functional integration are inherent to receptor protein kinases•Lipid membrane is inalienable part of the self-consistent signaling system•Cytoskeleton remodeling and membrane shaping attune receptor protein kinase activity