title: Integrins interact with focal adhesions through multiple distinct pathways.
abstract: Integrin signaling involves oligomerization and a transmembrane conformational change induced by receptor occupancy. Previous work has shown that subsets of focal adhesion-associated proteins are recruited to integrins as a result of clustering, ligand binding, or both. However, it is unclear whether these discrete subsets reflect the differential binding of cytoplasmic proteins to the integrin or whether a single protein or set of proteins binds the integrin and is differentially activated by receptor occupancy or clustering. To address this question, we made mutations of the beta1 integrin cytoplasmic domain in the context of a single subunit chimera and studied their activation of various known integrin-mediated signaling pathways. We show here that the indirect association of the integrin with actin is distinct from its interactions with both preformed focal adhesions and FAK. Therefore, multiple independent signaling pathways exist from the integrin to the focal adhesion, which may reflect the association of independent factors with the integrin beta1 cytoplasmic domain.
authors.affiliation: Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: F S
authors.initials: FS
authors.lastname: David
authors.forename: P E
authors.initials: PE
authors.lastname: Zage
authors.forename: E E
authors.initials: EE
authors.lastname: Marcantonio
mesh_terms: D000199:Actins / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002645:Chickens; D003593:Cytoplasm / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000267:Tissue Adhesions / Q000503:physiopathology*
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D016023:Integrins; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases