The human tumour suppressor LATS1 is activated by human MOB1 at the membrane

Biochem Biophys Res Commun. 2006 Jun 23;345(1):50-8. doi: 10.1016/j.bbrc.2006.03.244. Epub 2006 Apr 25.


Downregulation of the LATS1 tumour suppressor protein kinase contributes to tumour formation in mammals and flies. Strikingly, the tumour suppressor activity depends on the interaction with Dmob (Drosphila Mps1-One binder) in Drosophila melanogaster. Recently, human LATS1 was reported to interact with human MOB1 (hMOB1), but the activation of LATS1 was not addressed. Here, we identified a highly conserved hMOB1-binding motif within LATS1's primary structure. While co-expression of LATS1 with hMOB1 did not elevate LATS1 kinase activity in mammalian cells, membrane-targeting of hMOB1 resulted in a significant increase of LATS1 activity. This stimulation was dependent on intact activation segment and hydrophobic motif phosphorylation sites, and was further found to occur a few minutes after membrane association. Therefore, we suggest a potential in vivo mechanism of LATS1 activation through rapid recruitment to the plasma membrane by hMOB1 followed by multi-site phosphorylation, thereby providing insight into the molecular regulation of the LATS tumour suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Binding Sites
  • COS Cells
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Chlorocebus aethiops
  • Conserved Sequence
  • Enzyme Activation
  • Humans
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • MOB1A protein, human
  • MOB1B protein, human
  • LATS1 protein, human
  • Protein-Serine-Threonine Kinases