title: Structural insights into the recognition of β3 integrin cytoplasmic tail by the SH3 domain of Src kinase.
abstract: Src kinase plays an important role in integrin signaling by regulating cytoskeletal organization and cell remodeling. Previous in vivo studies have revealed that the SH3 domain of c-Src kinase directly associates with the C-terminus of β3 integrin cytoplasmic tail. Here, we explore this binding interface with a combination of different spectroscopic and computational methods. Chemical shift mapping, PRE, transferred NOE and CD data were used to obtain a docked model of the complex. This model suggests a different binding mode from the one proposed through previous studies wherein, the C-terminal end of β3 spans the region in between the RT and n-Src loops of SH3 domain. Furthermore, we show that tyrosine phosphorylation of β3 prevents this interaction, supporting the notion of a constitutive interaction between β3 integrin and Src kinase.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut.
authors.forename: Priya
authors.initials: P
authors.lastname: Katyal
authors.forename: Robbins
authors.initials: R
authors.lastname: Puthenveetil
authors.forename: Olga
authors.initials: O
authors.lastname: Vinogradova
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D039661:Integrin beta3 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D039661:Integrin beta3; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)
keywords: NMR; Src-kinase; integrin
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