Research Papers: Pathology:
The SRC-family tyrosine kinase HCK shapes the landscape of SKAP2 interactome
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Jean-François Bureau1,2, Patricia Cassonnet3,4,5, Laura Grange1,2, Julien Dessapt1,2, Louis Jones3,4,5, Caroline Demeret3,4,5, Anavaj Sakuntabhai1,2 and Yves Jacob3,4,5
1Unité de Génétique Fonctionnelle des Maladies Infectieuses, Département Génome et Génétique, Institut Pasteur, Paris, France
2CNRS URA3012, Paris, France
3Unité de Génétique Moléculaire des Virus à ARN, Département Virologie, Institut Pasteur, Paris, France
4UMR3569, Centre National de la Recherche Scientifique, Paris, France
5Université Paris Diderot, Paris, France
Jean-François Bureau, email: [email protected]
Yves Jacob, email: [email protected]
Keywords: luciferase complementation assay; protein-protein interaction; SRC-kinase family; adaptor; FYB; Pathology
Received: November 16, 2017 Accepted: January 30, 2018 Published: February 06, 2018
The SRC Kinase Adaptor Phosphoprotein 2 (SKAP2) is a broadly expressed adaptor associated with the control of actin-polymerization, cell migration, and oncogenesis. After activation of different receptors at the cell surface, this dimeric protein serves as a platform for assembling other adaptors such as FYB and some SRC family kinase members, although these mechanisms are still poorly understood. The goal of this study is to map the SKAP2 interactome and characterize which domains or binding motifs are involved in these interactions. This is a prerequisite to finely analyze how these pathways are integrated in the cell machinery and to study their role in cancer and other human diseases when this network of interactions is perturbed. In this work, the domain and the binding motif of fourteen proteins interacting with SKAP2 were precisely defined and a new interactor, FAM102A was discovered. Herein, a fine-tuning between the binding of SRC kinases and their activation was identified. This last process, which depends on SKAP2 dimerization, indirectly affects the binding of FYB protein. Analysis of conformational changes associated with activation/inhibition of SRC family members, presently limited to their effect on kinase activity, is extended to their interactive network, which paves the way for therapeutic development.
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