Nck interaction partners: Molecular interactions and functional consequences

• Applicant: Dr. Marcus Lettau
• Subject Area: Immunology
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 205834279

As a prototypical adapter protein Nck is almost completely built of three Src homology (SH) 3 domains and a single SH2 domain. A main function of Nck is to link receptor-associated tyrosine kinases with proteins regulating the actin cytoskeleton. Nck is functionally associated with a plethora of different processes including the development and maintenance of tissue integrity, the activation and effector function of immune cells, but also malignant transformation and invasivity of tumour cells. Importantly, all these processes rely on changes of cell polarity, morphology and migration and can be regulated by Nck-associated protein complexes. Furthermore, recent studies suggested a role of Nck in the regulation of cellular proliferation relying on a nuclear translocation of Nck. In previous work of our group, we identified the actin-binding adapter protein HIP55 and ADAP, which has been implicated in integrin signalling, as Nck-interacting proteins. Moreover, with the heterodimeric splicing factor SFPQ/NONO, we also described a nuclear binding partner for Nck. In the proposed project, we want to further characterize the role of the interactions of Nck with ADAP and HIP55, especially in the T cell compartment. Furthermore, we want to verify the interaction with SFPQ/NONO and the nuclear translocation of Nck and investigate the putative function of nuclear Nck and SFPQ/NONO.

• DFG Programme: Research Grants