Tag and Loading Control Antibodies
Molecular Biology Reagents
Nucleic Acid Modifying Enzymes
Hippo signaling is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, apoptosis, and stem cell self-renewal. In addition, dysregulation of the Hippo pathway contributes to cancer development.The Core of the Mammalian Hippo Pathway
Similar to the invertebrate cascade, a series of phosphorylation events via MST (ortholog of Drosophila Hippo) and Wts (mammalian LATS1/2) ultimately leads to the phosphorylation of two co-activators: YAP and TAZ. Once phosphorylated, the protein kinase is activated, resulting in a series of changes in downstream processes.Activation of the Mammalian Hippo Pathway
Yorkie (Yki) is a transcriptional co-activator; it cannot be directly combined with DNA, but needs to combine with the transcription factor Scalloped (Sd) to form the Yki-Sd complex, which plays a role in transcription regulation. The Yki-Sd transcription complex can be regulated by multiple genes related to cell proliferation and transcription regulation, such as E cyclin. When the organ reaches a certain size, the pathway is activated and phosphorylated (activated) Wts can be phosphorylated by Yki, and the 168th serine is activated. Yki binds to 14-3-3 after phosphorylation (inactivation). This process allows Yki to reside in the cytoplasm, which cannot form a transcriptional regulatory complex with Sd, and inhibit the transcription of downstream target genes.
In the nucleus, both YAP and TAZ can bind to TEAD1/4 and activate the transcription of genes required to promote cell growth and inhibit apoptosis (CTGF, AREG, BIRC5-2, FGF, and GLI-2). Upon phosphorylation by the SRC/ABL kinases, YAP and TAZ acquire the capacity to bind p73 and activate the transcription of proapoptotic genes. Numerous transcription factors are described as YAP/TAZ binding partners, but their functional significance is still unclear.