It is a positive regulator of this pathway and binds to many proteins in the pathway, including all three kinases in the cascade. One such scaffold protein is KSR1, which is most likely a well-studied yeast MAPK scaffold protein Ste5. Several scaffold proteins have been identified to be involved in this pathway and other similar MAPK pathways. One of the best studied signaling pathways in biology is the RAS-ERK pathway, in which the RAS G protein activates MAPKKK RAF, which activates MAPKK MEK1 (MAPK / ERK kinase 1) and then activates MAPK ERK. The kinase inhibitor of Ras 1 is an enzyme encoded by the KSR1 gene in humans. These functions may be related to the response between scaffold proteins and kinases, the underlying phosphatase activity in cells, the stability of expression levels of scaffold proteins and signaling components. In a triple kinase signal tandem, scaffold proteins bind to all three kinases, enhance kinase specificity, and limit kinase phosphorylation by limiting kinase phosphorylation to a downstream target. Many hypotheses about how scaffold proteins assist positive and negative feedback regulation come from synthetic scaffold proteins and mathematical modeling. Assist positive feedback and negative feedback adjustment Such localization can locally regulate PKA so that PKA can phosphorylate its substrate in a localized region.ģ. A particular example is the A-type kinase-anchored protein ( AKAP), which localizes the cyclic adenylate-dependent protein kinase (ie, protein kinase A, PKA) at different locations in the cell. Scaffold proteins localize signal components in specific regions of the cell, a process that is important in the local production of signal intermediates. Localization of signal components in cells The interaction of a signaling protein with a scaffold protein may also result in an allosteric change in the signaling protein, thereby enhancing or inhibiting the activation process therefore, some scaffolding may be referred to as catalytic scaffolding.Ģ. Because certain signaling proteins require multiple interactions to activate, scaffold proteins can facilitate the transformation of the distribution process. For example, a scaffold can act to enhance the phosphorylation specificity of a kinase by binding to a protein kinase and its substrate. This can increase the efficiency of signaling concatenation by centralizing signaling components and can enhance signaling specificity by preventing false interactions between them. The most basic function of the scaffold protein is the assembly of the cascaded signal components. These functions of scaffold proteins can provide additional complexity for signal cascades and generate signal thresholds or adjust complex signal transmission behaviors such as hierarchical or digital signal transmission, transient or continuous signal transmission, and oscillating signal transmission.įigure 1. Inactivate the activation signal molecule. These methods indicate that the scaffold can function in at least four aspects: by acting as a platform on which the signal molecule can be assembled, by locating the signal molecule at a specific site in the cell, by aligning the positive feedback signal with the negative feedback signal Signal pathways and protect cells to function. Most of our understanding of scaffold protein function comes from mathematical modeling and engineering of scaffold proteins. In these signaling pathways, scaffold proteins regulate signal transduction and localize pathway components (in the form of complexes) to specific regions of the cell, such as cell membranes, cytoplasmic stroma, nucleus, Golgi, endosomes, and mitochondria. Although the functions of scaffold proteins are not strictly defined, they interact or combine with multiple components in the signaling pathway to form a complex. In biology, scaffold proteins are important regulators in many key signaling pathways.
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