Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling.
The NDR/LATS family of kinases is a subgroup of the AGC group of protein kinases and is conserved from lower eukaryotes to humans. Like other AGC kinases, NDR/LATS kinases require phosphorylation of conserved Ser/Thr residues for activation. On the one hand, binding of the coactivator MOB to NDR/LATS allows autophosphorylation. On the other hand, MST kinases directly phosphorylate NDR/LATS kinases. In addition to our understanding of the molecular activation mechanisms, recent studies have shown that LATS kinases play a central role in Hippo/SWH (Salvador/Warts/Hippo) tumor suppressor pathways, which coordinate cell proliferation and apoptosis by regulating proto-oncogenes, such as YAP and TAZ. In this review, we summarize current knowledge of Merlin/MST/SAV/MOB/LATS/NDR/YAP/TAZ networks (also termed mammalian Hippo signaling) and their roles in mammalian cellular transformation.
Hergovich
Alexander
A
Friedrich Miescher Institute for Biomedical Research, Growth Control, Maulbeerstrasse 66, Basel, Switzerland. hergo@fmi.ch
Hemmings
Brian A
BA
D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D025581:Neurofibromin 2 / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology; D000099317:Hippo Kinases
D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D025581:Neurofibromin 2; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C496256:MOB1A protein, human; C496255:MOB1B protein, human; C415864:SAV1 protein, human; C456659:YY1AP1 protein, human; C108675:TAFAZZIN protein, human; C092745:LATS1 protein, human; C430908:STK26 protein, human; D000099317:Hippo Kinases; C406449:LATS2 protein, human; C095566:STK4 protein, human; C097835:STK3 protein, human; C491614:STK38 protein, human; C496014:STK38L protein, human; C499474:hpo protein, Drosophila