Casar, B., Arozarena, I., Sanz-Moreno, V., Pinto, A., Agudo-Ibanez, L., Marais, R., Lewis, R.(2009) KSR2 is a calcineurin substrate that promotes ERK cascade activation in response to calcium signals. (1996) KSR modulates signal propagation within the MAPK cascade. (2004) Sef is a spatial regulator for Ras/MAP kinase signaling. Torii, S., Kusakabe, M., Yamamoto, T., Maekawa, M., and Nishida, E.(2004) Paxillin serves as an ERK-regulated scaffold for coordinating FAK and Rac activation in epithelial morphogenesis. (2005) IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. (1998) MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. (2005) Coordinating ERK/MAPK signalling through scaffolds and inhibitors. (2003) Regulation of MAP kinase signaling modules by scaffold proteins in mammals. (2006) The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. (2007) The MEK/ERK cascade: from signaling specificity to diverse functions. Window.SHOGUN_IMAGE_ELEMENTS = window.SHOGUN_IMAGE_ELEMENTS || new Array() An intermediate or optimal concentration of scaffold results in higher signalling. Combinatorial inhibition occurs when there is too little scaffold or too much scaffold lowering the signalling of a pathway. The effect of expressing scaffold protein on the MAPK pathway signalling (Ferrell 2000). In mammalians, the best characterised scaffold is KSR1 which is the homologue of Ste5 and also functions by assembling members of the MAPK proteins to increase MAPK signalling (Therrien et al. The functions of scaffolds has been helped by studies on yeast of the the protein Ste5 which regulates the MAPK pathway (Zalatan et al. Too little scaffold causes the signal to be low and too high scaffold concentration cause binding partners to be titrated away from one another, thus decreasing the signal output (Levchenko et al. An optimal concentration of scaffold is required, otherwise scaffolds inhibit pathways in a process called combinatorial inhibition (Ferrell 2000). The diagram represents how a change in scaffold concentration regulates the activity of the cell signalling pathway it scaffolds. 2011).Īctivation of signalling pathways by scaffold proteins induces a bell shaped curve activation. The scaffold concentration is crucial in regulating cell signalling pathways and results in the activation of a signalling pathway, which resembles a bell shaped curve (Adams et al. Due to the absent of enzymatic activity, to test whether a protein is scaffolding a particular pathway we must increase the amount of the scaffold protein and look at the output activity of the cell signalling pathway. 2015) Importantly, classical scaffolds lack enzymatic activity but can enhance the efficiency of a signalling pathway by assembling the core components of a pathway (Adams et al. Scaffold proteins compartmentalize and coordinate signalling events by serving as a platform that regulates protein-protein interactions (Abel et al. Scaffold proteins function by assembling the components of signalling pathway into one complex and this increases the efficiency of the signalling pathway (Levchenko et al. Scaffold proteins localize partners of a pathway to specific areas of the cell and by protecting cell signalling pathways from phosphatases (Good et al. They act by interacting with proteins of a signalling pathway to tether multiple proteins into a complex that regulates the activity of signalling pathways (Shaw and Filbert 2009). Scaffold proteins are evolutionarily conserved proteins that play important roles in coordinating signalling events in eukaryotic cells (Abel et al. How cells translate specific stimuli into a specific cellular response is not well understood. Environmental stimuli result in different biological responses including cell growth, proliferation or apoptosis.
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