Details

Autor(en) / Beteiligte

• Yu, Fa-Xing
• Zhang, Yifan
• Park, Hyun Woo
• Jewell, Jenna L
• Chen, Qian
• Deng, Yaoting
• Pan, Duojia
• Taylor, Susan S
• Lai, Zhi-Chun
• Guan, Kun-Liang

Titel

Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation

Ist Teil von

• Genes & development, 2013-06, Vol.27 (11), p.1223-1232

Ort / Verlag

United States: Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.