Thus, the ligase-deficient mutant T6Rm cannot activate TAK1 during TLR signaling.
RIN1QM, a mutant that cannot activate ABL but still activates RAB5, caused dominant suppression of EGF-induced ABL kinase activation and accelerated EGFR degradation.
Thus, one possible explanation for the loss of inflammasome activation observed in the PA103ΔUΔT pilA- mutant is that it fails to attach to macrophages and cannot mediate type III secretion, hence behaving like the pcrV- mutant, which cannot activate the inflammasome.
In particular, mutants that cannot activate σF but are properly localized would be expected to oligomerize properly.
The RIN1 GEF domain mutant RIN1E574A, which cannot activate RAB5 but can still activate ABL, suppressed RAB5 activity in a dominant negative manner and blocked EGFR degradation while it promoted receptor recycling.
The T172D mutant cannot be phosphorylated and activated by upstream kinases but has significant activity and retains allosteric activation by AMP (Stein et al., 2000).
In agreement with the GST pull-down results, our kinetic data show that the GEF activity of the L434D, L438D, and W441A Rabex-5 mutants cannot be activated by Rabaptin-5C21, whereas that of the I439D Rabex-5 mutant can be potentiated by Rabaptin-5C21.
Thus, flagellin-deficient mutants of S. Typhimurium cannot activate caspase-1 directly and they fail to deploy T1 or inject SopE, because they do not efficiently reach the host cell.
They are also similar in that they utilize the antigen receptor to transmit their signals to the cell since CD3-TCR mutants cannot be activated via either CD2 or the toxin receptor.
Oestrogen receptor alpha-3 and ER α-6 clones overexpress wild-type ER α, whereas ER α-8 and ER α-9 overexpress mutant ER α (C530R), which cannot activate transcription of an ERE-containing reporter gene (data not shown).
