MAPK signalling regulation and cancer: lessons from fission yeast

Published on October 18, 2015   37 min

A selection of talks on Cell Biology

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0:00
Hello. I'm Reiko Sugiura of the Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences, Kinki University. I'd like to talk about "MAPK Signaling Regulation and Cancer, Lessons from Fission Yeast."
0:17
First, I'll give you a overview of MAPK signaling. Second, I'll introduce our molecular genetic approach to identify regulators with MAPK signaling. Third, I'll explain how we applied our chemical genomic screen to identify inhibitors of MAPK signaling. And finally, I'd like to discuss the physiological and the medical implications of this regulation in human diseases, including cancers.
0:47
This is a scheme of the MAPK signaling cascade. This mitogen-activated protein, kinase, or a MAPK cascade is a highly conserved signaling module that is involved in various cellular functions including cell proliferation, differentiation and migration. MAPK pathways consist of a series of at least three kinases, extracellular stimulus, such as growth factors and environmental stresses induced the sequential activation of MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. The MAP kinase is activated by a unique way. MAP kinases are activated by phosphorylation on both the threonine and tyrosine residues over a conserved signature, TxY motif within the activation loop of the kinase. This is carried out by an upstream dual-specificity MAP kinase kinase, which is in turn regulated by phosphorylation of serine and threonine residues by a MAPKKK. Since phosphorylation is required for the activation of MAP kinases, the phosphorylation of MAPKs by members of the MAP kinase phosphatase family plays a critical role in negative re-regulating of MAPK signaling and transduction pathway. This can be achieved by serine and threonine phosphatases, tyrosine-specific phosphatases or by dual-specificity phosphatases. Studies in a wide variety of modules, from yeast to man have demonstrated that all three major classes of protein phosphatases can perform this task in vivo.

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MAPK signalling regulation and cancer: lessons from fission yeast

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