TSAd as a modulator of immune cell signalling

A key challenge and a major opportunity in modern medicine is to exploit and control the patients' own immune responses to treat disease. The overall aim of this project is to delineate one molecular mechanism by which signalling molecules crucial for immune cell function are controlled. We have previously found that TSAd is a crucial modulator of the immune specific tyrosine kinases Lck and Itk. These intra cellular enzymes are potent proto-oncogenes, and a number of mechanisms have evolved to control their activity. In the present project we perform a detailed characterization of TSAd´s ability to promote molecular crosstalk between Lck and Itk and the functional consequences thereof. The project has now gone on for slighly more than two years. During this time we have analysed in detail the molecular crosstalk between TSAd, Lck and Itk. We have identified critical tyrosines in all three molecules that are important for keeping these three molecules stick together in one complex. The research contributes to a comprehensive understanding of how key cellular signalling molecules are regulated in immune cells, and this insight will open new possibilities for treatment of disease.

A key challenge and a major opportunity in modern medicine is to exploit and control the patients' own immune responses to treat disease. The overall aim of this project is to delineate one molecular mechanism by which signalling molecules crucial for imm une cell function are controlled. The adapter protein TSAd is involved in control of differentiation of T cells and epithelial cells, which possibly impacts on development of cancer and autoimmune disease. A key to understand the function of TSAd and its potential as a target for therapies against cancer and autoimmune disease is to delineate the protein interaction network that TSAd is a part of. We have previously found that TSAd is a crucial modulator of the immune specific tyrosine kinases Lck and I tk. These intra cellular enzymes are potent proto-oncogenes, and a number of mechanisms have evolved to control their activity. In the present project we will perform a detailed characterization of TSAd´s ability to promote molecular crosstalk between Lck and Itk and the functional consequences thereof. The research will contribute to a comprehensive understanding of how key cellular signalling molecules are regulated in immune cells, and this insight will open new possibilities for treatment of disease.