Yu, F.X., Zhang, Y., Park, H.W., Jewell, J.L., Chen, Q., Deng, Y., Pan, D., Taylor, S.S., Lai, Z.C., Guan, K.L. (2013). Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation.  Genes Dev. 27(11): 1223--1232.

FBrf0221762

Research paper

The Hippo tumor suppressor pathway plays an important role in tissue homeostasis that ensures development of functional organs at proper size. The YAP transcription coactivator is a major effector of the Hippo pathway and is phosphorylated and inactivated by the Hippo pathway kinases Lats1/2. It has recently been shown that YAP activity is regulated by G-protein-coupled receptor signaling. Here we demonstrate that cyclic adenosine monophosphate (cAMP), a second messenger downstream from Gαs-coupled receptors, acts through protein kinase A (PKA) and Rho GTPases to stimulate Lats kinases and YAP phosphorylation. We also show that inactivation of YAP is crucial for PKA-induced adipogenesis. In addition, PKA activation in Drosophila inhibits the expression of Yorki (Yki, a YAP ortholog) target genes involved in cell proliferation and death. Taken together, our study demonstrates that Hippo-YAP is a key signaling branch of cAMP and PKA and reveals new insight into mechanisms of PKA in regulating a broad range of cellular functions.

PMC3690396 (PMC) (EuropePMC)