Michael F. Ritchie

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Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca(2+) signaling. However, precisely how oxidants influence Ca(2+) signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca(2+) mobilization from(More)
T-cell activation involves a complex signalling cascade uniquely dependent on elevated cytosolic Ca(2+) levels. Further, the spatiotemporal characteristics of this Ca(2+) signal play a critical role in this process via selective activation of transcription factors. In T cells, store-operated Ca(2+) entry (SOCe) is the primary Ca(2+) influx pathway; however,(More)
STIM proteins are sensors of endoplasmic reticulum (ER) luminal Ca(2+) changes and rapidly translocate into near plasma membrane (PM) junctions to activate Ca(2+) entry through the Orai family of highly Ca(2+)-selective "store-operated" channels (SOCs). Dissecting the STIM-Orai coupling process is restricted by the abstruse nature of the ER-PM junctional(More)
STIM1 and STIM2 are dynamic transmembrane endoplasmic reticulum Ca(2+) sensors, coupling directly to activate plasma membrane Orai Ca(2+) entry channels. Despite extensive sequence homology, the STIM proteins are functionally distinct. We reveal that the short variable N-terminal random coil sequences of STIM1 and STIM2 confer profoundly different(More)
Store-operated calcium entry (SOCE) is a key evolutionarily conserved process whereby decreases in endoplasmic reticulum Ca(2+) content lead to the influx of Ca(2+) across the plasma membrane. How this process is regulated in specific tumor cell types is poorly understood. In an effort to address this concern, we obtained and tested primary Wilms tumor(More)
Store-operated channels (SOCs) mediate Ca(2+) entry signals in response to endoplasmic reticulum (ER) Ca(2+) depletion in most cells. STIM1 senses decreased ER luminal Ca(2+) through its EF-hand Ca(2+)-binding motif and aggregates in near-plasma membrane (PM) ER junctions to activate PM Orai1, the functional SOC. STIM1 is also present in the PM, although(More)
T-cell activation involves a complex signalling cascade uniquely dependent on elevated cytosolic Ca levels. Further, the spatiotemporal characteristics of this Ca signal play a critical role in this process via selective activation of transcription factors. In T cells, store-operated Ca entry (SOCe) is the primary Ca influx pathway; however, cytosolic Ca(More)
Ca(2+) is a dynamic cellular secondary messenger which mediates a vast array of cellular responses. Control over these processes is achieved via an extensive combination of pumps and channels which regulate the concentration of Ca(2+) within not only the cytosol but also all intracellular compartments. Precisely how these pumps and channels are regulated is(More)
There have been numerous publications linking Ca(2+) signaling and cancer, however, a clear explanation for this link has remained elusive. We recently identified the oncogenes/tumor suppressors Wilms Tumor Suppressor 1 (WT1) and Early Growth Response 1 (EGR1) as regulators of the expression of STIM1, an essential regulator of Ca(2+) entry in non-excitable(More)
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