title: Proteomic analysis of integrin adhesion complexes.
abstract: Integrin receptors regulate cell fate by coupling the binding of extracellular adhesion proteins to the assembly of intracellular cytoskeletal and signaling complexes. A detailed, integrative view of adhesion complexes will provide insight into the molecular mechanisms that control cell morphology, survival, movement, and differentiation. To date, membrane receptor-associated signaling complexes have been refractory to proteomic analysis because of their inherent lability and inaccessibility. We developed a methodology to isolate ligand-induced integrin adhesion complexes, and we used this technique to analyze the composition of complexes associated with multiple receptor-ligand pairs and define core and receptor-specific subnetworks. In particular, we identified regulator of chromosome condensation-2 (RCC2) as a component of fibronectin-activated signaling pathways that regulate directional cell movement. The development of this proteomics pipeline provides the means to investigate the molecular composition and function of various adhesion complexes.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Byron
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Humphries
authors.forename: Mark D
authors.initials: MD
authors.lastname: Bass
authors.forename: David
authors.initials: D
authors.lastname: Knight
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Humphries
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D016000:Cluster Analysis; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; D002868:Chromosomal Proteins, Non-Histone; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins; D046912:Multiprotein Complexes; C477650:RCC2 protein, human