Antigen presentation to the T-cell receptor leads to sustained cytosolic Ca elevation， which is critical for T-cell activation. We previously showed that in activated T cells， Ca clearance is inhibited by the endoplasmic reticulum Ca sensor stromal interacting molecule 1 (STIM1) via association with the plasma membrane Ca/ATPase 4 (PMCA4) Ca pump. Having further observed that expression of both proteins is increased in activated T cells， the current study focused on mechanisms regulating both up-regulation of STIM1 and PMCA4 and assessing how this up-regulation contributes to control of Ca clearance. Using a STIM1 promoter luciferase vector， we found that the zinc finger transcription factors early grow... More
Antigen presentation to the T-cell receptor leads to sustained cytosolic Ca elevation， which is critical for T-cell activation. We previously showed that in activated T cells， Ca clearance is inhibited by the endoplasmic reticulum Ca sensor stromal interacting molecule 1 (STIM1) via association with the plasma membrane Ca/ATPase 4 (PMCA4) Ca pump. Having further observed that expression of both proteins is increased in activated T cells， the current study focused on mechanisms regulating both up-regulation of STIM1 and PMCA4 and assessing how this up-regulation contributes to control of Ca clearance. Using a STIM1 promoter luciferase vector， we found that the zinc finger transcription factors early growth response (EGR) 1 and EGR4， but not EGR2 or EGR3， drive luciferase activity. We further found that neither STIM1 nor PMCA4 is up-regulated when both EGR1 and EGR4 are knocked down using RNA interference. Further， under these conditions， activation-induced Ca clearance inhibition was eliminated with little effect on Ca entry. Finally， we found that nuclear factor of activated T-cell (NFAT) activity is profoundly attenuated if Ca clearance is not inhibited by STIM1. These findings reveal a critical role for STIM1-mediated control of Ca clearance in NFAT induction during T-cell activation.-Samakai， E.， Hooper， R.， Martin， K. A.， Shmurak， M.， Zhang， Y.， Kappes， D. J.， Tempera， I.， Soboloff， J. Novel STIM1-dependent control of Ca clearance regulates NFAT activity during T-cell activation.
