| First Author | Lin TY | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 12 | Pages | 113535 |
| PubMed ID | 38060450 | Mgi Jnum | J:350331 |
| Mgi Id | MGI:7574055 | Doi | 10.1016/j.celrep.2023.113535 |
| Citation | Lin TY, et al. (2023) Epinephrine inhibits PI3Kalpha via the Hippo kinases. Cell Rep 42(12):113535 |
| abstractText | The phosphoinositide 3-kinase p110alpha is an essential mediator of insulin signaling and glucose homeostasis. We interrogated the human serine, threonine, and tyrosine kinome to search for novel regulators of p110alpha and found that the Hippo kinases phosphorylate p110alpha at T1061, which inhibits its activity. This inhibitory state corresponds to a conformational change of a membrane-binding domain on p110alpha, which impairs its ability to engage membranes. In human primary hepatocytes, cancer cell lines, and rodent tissues, activation of the Hippo kinases MST1/2 using forskolin or epinephrine is associated with phosphorylation of T1061 and inhibition of p110alpha, impairment of downstream insulin signaling, and suppression of glycolysis and glycogen synthesis. These changes are abrogated when MST1/2 are genetically deleted or inhibited with small molecules or if the T1061 is mutated to alanine. Our study defines an inhibitory pathway of PI3K signaling and a link between epinephrine and insulin signaling. |
