Research ResourceSystems Biology

Protein Interaction Network of the Mammalian Hippo Pathway Reveals Mechanisms of Kinase-Phosphatase Interactions

See allHide authors and affiliations

Science Signaling  19 Nov 2013:
Vol. 6, Issue 302, pp. rs15
DOI: 10.1126/scisignal.2004712

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Switching Partners in the Hippo Pathway

The Hippo kinase cascade, named for the large size of flies in which it was originally identified, is an evolutionarily conserved pathway that regulates cell proliferation during organogenesis. Couzens et al. used two different proteomic methods to define a protein interaction network surrounding the core proteins of the Hippo pathway. Mutational analysis and proteomic profiling of protein interactions that changed with pharmacological inhibition of phosphatase activity revealed that many interactions within the Hippo protein interaction network are governed by the phosphorylation status of serine and threonine residues. Members of the MOB1 kinase adaptor family that are known to bind the kinase LATS switched from interacting with positive components of the pathway, such as the kinases upstream of LATS, MST1 and MST2, early during phosphatase inhibition to interacting with putative negative pathway regulators, such as protein phosphatase 6, later during phosphatase inhibition. These results emphasize the importance of considering dephosphorylation as a key mechanism regulating Hippo signaling.

View Full Text

Stay Connected to Science Signaling