LKB1 tumor suppressor protein: PARtaker in cell polarity.
The LKB1 (also called serine/threonine kinase 11) tumor suppressor gene was cloned in 1998 by linkage analysis of Peutz-Jeghers cancer syndrome patients. Mammalian LKB1 has been implicated as a regulator of multiple biological processes and signaling pathways, including the control of cell-cycle arrest, p53-mediated apoptosis, Wnt signaling, transforming growth factor (TGF)-beta signaling, ras-induced cell transformation, and energy metabolism. The Caenorhabditis elegans and Drosophila melanogaster LKB1 homologs, termed PAR4 and dLKB1, respectively, regulate cell polarity. Recently, mammalian LKB1 was found to be active only in a complex with two other proteins--STRAD and MO25--and to induce complete polarization of intestinal epithelial cells in a cell-autonomous fashion. In this article, we summarize the findings regarding LKB1 over the past six years. In addition, we discuss LKB1 in polarity in the context of both the other PAR proteins and its tumor suppressive activities.
Baas
Annette F
AF
Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Smit
Linda
L
Clevers
Hans
H
D055372:AMP-Activated Protein Kinases; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases