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The disequilibrium caused by these changes often causes withdrawal when the long-term use of a drug is discontinued. Upregulation and downregulation can also happen as a response to toxins or hormones. An example of upregulation in pregnancy is hormones that cause cells in the uterus to become more sensitive to oxytocin.
Unsuccessful protein folding can be caused by HLA-B27, disturbing balance of important (IL-10 and TNF) signaling proteins. At least some disturbances are reliant on correct HLA-B27 folding. [12] However, where circumstances cause a more global disruption to protein folding that overwhelms the ER's coping mechanisms, the UPR is activated.
In the post-genomic age, high-throughput sequencing and gene/protein profiling techniques have transformed biological research by enabling comprehensive monitoring of a biological system, yielding a list of differentially expressed genes or proteins, which is useful in identifying genes that may have roles in a given phenomenon or phenotype. [120]
This particular function is considered a scaffold's most basic function. Scaffolds assemble signaling components of a cascade into complexes. This assembly may be able to enhance signaling specificity by preventing unnecessary interactions between signaling proteins, and enhance signaling efficiency by increasing the proximity and effective concentration of components in the scaffold complex.
Low-affinity binding (high K i level) implies that a relatively high concentration of a ligand is required before the binding site is maximally occupied and the maximum physiological response to the ligand is achieved. In the example shown to the right, two different ligands bind to the same receptor binding site.
Two similar protein kinases with 85% sequence identity were originally called ERK1 and ERK2. [2] They were found during a search for protein kinases that are rapidly phosphorylated after activation of cell surface tyrosine kinases such as the epidermal growth factor receptor. Phosphorylation of ERKs leads to the activation of their kinase activity.
The signal that starts the MAPK/ERK pathway is the binding of extracellular mitogen to a cell surface receptor. This allows a Ras protein (a Small GTPase) to swap a GDP molecule for a GTP molecule, flipping the "on/off switch" of the pathway. The Ras protein can then activate MAP3K (e.g., Raf), which activates MAP2K, which activates MAPK.
It is known that rapid heat hardening can be elicited by a brief exposure of cells to sub-lethal high temperature, which in turn provides protection from subsequent and more severe temperature. In 1962, Italian geneticist Ferruccio Ritossa reported that heat and the metabolic uncoupler 2,4-dinitrophenol induced a characteristic pattern of ...