کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2830840 | 1163762 | 2014 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The adapter proteins ADAP and Nck cooperate in T cell adhesion The adapter proteins ADAP and Nck cooperate in T cell adhesion](/preview/png/2830840.png)
• Nck interacts with tyrosine Y595DDV and Y651DDV sites of ADAP via its SH2 domain.
• The Nck/ADAP interaction is enhanced upon TCR stimulation in human T cell blasts.
• Nck and ADAP functionally cooperate in T cell adhesion to ICAM-1.
Nck adapter proteins link receptor and receptor-associated tyrosine kinases with proteins implicated in the regulation of the actin cytoskeleton. Nck is involved in a multitude of receptor-initiated signaling pathways and its physiological role thus covers aspects of tissue development and homeostasis, malignant transformation/invasiveness of tumour cells and also immune cell function. In T cells, changes of cell polarity and morphology associated with cellular activation and effector function crucially rely on the T cell receptor-mediated recruitment and activation of different actin-regulatory proteins to orchestrate and drive cytoskeletal reorganization at the immunological synapse. In a former approach to determine the interactome of Nck in human T cells, we identified the adapter protein ADAP as a Nck-interacting protein. This adhesion and degranulation-promoting adapter protein had already been implicated in the inside-out activation of integrins. Employing co-immunoprecipitations, we demonstrate that both Nck family members Nck1 and Nck2 coprecipitate with ADAP. Specifically, Nck interacts via its Src homology 2 domain with phosphorylated tyrosine Y595DDV and Y651DDV sites of ADAP. Moreover, we show that endogenous ADAP is phosphorylated in primary human T cell blasts and thus associates with Nck. At the functional level, ADAP and Nck adapter proteins cooperatively facilitate T cell adhesion to the LFA-1 ligand ICAM-1. Our data indicate that the ADAP/Nck complex might provide a means to link integrin activation with the actin cytoskeleton.
Journal: Molecular Immunology - Volume 60, Issue 1, July 2014, Pages 72–79