Article Abstract:
A common enzyme found to connect Notch signaling and Alzheimer's disease is discussed in this review article. A novel class of enzymes for which there is now good evidence is made up of polytopic membrane proteins that can catalyze the intramembrane hydrolysis of a peptide bond and the presenilin proteins (PS), mostly in intracellular membranes, are founding members of the protease class. Topics include beta-amyloid precursor protein (APP) and the production of beta-amyloid, PS in the unfolded protein response (UPR) and PS as gamma-secretases.
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Article Abstract:
An SH2-domain-containing kinase has been found to regulate the phosphatidylinositol-3 kinase (PI3K) pathway negatively. It has been shown that SHK1 is necessary for proper phagocytosis and chemotaxis and it appears that SHK1 is necessary for the proper spatiotemporal control of F-actin levels in chemotaxing cells. SHK1 is localized at the plasma membrane/cortex.
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Article Abstract:
Mice lacking both presenilin genes are discussed, having been found to exhibit early embryonic patterning defects, which shows presenilins have a side role in embryogenesis. A functional redundancy exists with presenilin 1 (PS1) and presenilin 2 (PS2). Both vertebrate presenilins are essential for Notch signaling, as is the case with their invertebrate homologs. Delta like-1 and Hes-5, genes downstream in the Notch pathway, are misexpressed in embryos double-null for presenilin.
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