A study of DEF6 granule formation using biophysical and cellular methods
Mollett, Eleanor (2015) A study of DEF6 granule formation using biophysical and cellular methods. PhD thesis, University of Nottingham.
DEF6 is a Rho-Guanine Nucleotide Exchange Factor (GEF) with a poorly characterised role in T-cell receptor signalling and unknown structure1-3. Its importance in T-cell signalling has been highlighted by observations that DEF6-deficient T cells display defective actin polymerisation and polarisation, have a decreased susceptibility to CD3-induced apoptosis4, and exhibit aberrant expression of the inflammatory cytokine IL-172. DEF6 is a GEF for Rho-family GTPases including CDC42, RhoA and Rac11, which unlike other Rho-GEFs exhibits a reversal of the N-C terminal orientation of the DH and PH domains only found in DEF6 and its homolog in B-cells, SWAP70. Through this role DEF6 has been shown to be involved in the spatiotemporal organisation of T cell signalling through the GTPase CDC425. DEF6-deficient mice have been shown to develop autoimmune diseases and have also been shown to be resistant to the development of other autoimmune diseases, indicating a loss of control of the immune response. The molecular mechanism behind these phenotypes remains to be identified.
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