Abstract
Mammalian Ste20-like kinases 1 and 2 (MST1 and MST2) are activated in NIH3T3 cells exposed to okadaic acid. The Hippo pathway is a newly emerging signaling that functions as a tumor suppressor. MST1 and MST2 work as core kinases of the Hippo pathway and their activities depend on the autophosphorylation, which is negatively regulated by protein phosphatase 2A (PP2A). Okadaic acid has been frequently used to enhance the phosphorylation of MST1 and MST2 and to trigger the activation of the Hippo pathway. However other components of the Hippo pathway could also be targets of okadaic acid. In this review we first briefly summarize the molecular architecture of the Hippo pathway for the reference of researchers outside the field. We explain how MST kinases are regulated by PP2A and how okadaic acid activates MST2. Thereafter we discuss which components of the Hippo pathway are candidate substrates of protein phosphatases and which points we need to consider in the usage of okadaic acid to study the Hippo pathway.
Highlights
The Hippo pathway is a newly emerging tumor suppressor signaling [1,2]
MST1 and MST2 were identified as kinases that were activated in NIH3T3 cells by the treatment of okadaic acid [5]
It is necessary to consider that phosphatase 1 (PP1) and phosphatase 2A (PP2A) have a wide range of substrates, which are irrelevant of the Hippo pathway, and that okadaic acid may influence other phosphatases than
Summary
The Hippo pathway is a newly emerging tumor suppressor signaling [1,2]. It was originally identified in Drosophila as the signaling that regulates organ size. Mammalian Ste20-like kinases 1 and 2 (MST1 and MST2) are core components of the Hippo pathway. Okadaic acid has been widely used to experimentally activate the Hippo pathway. It is necessary to consider that PP1 and PP2A have a wide range of substrates, which are irrelevant of the Hippo pathway, and that okadaic acid may influence other phosphatases than. We will discuss the potential pitfalls in using okadaic acid as the activator of the Hippo pathway
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