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A role for Drosophila LKB1 in anterior–posterior axis formation and epithelial polarity


The PAR-4 and PAR-1 kinases are necessary for the formation of the anterior–posterior (A–P) axis in Caenorhabditis elegans1,2,3. PAR-1 is also required for A–P axis determination in Drosophila4,5. Here we show that the Drosophila par-4 homologue, lkb1, is required for the early A–P polarity of the oocyte, and for the repolarization of the oocyte cytoskeleton that defines the embryonic A–P axis. LKB1 is phosphorylated by PAR-1 in vitro, and overexpression of LKB1 partially rescues the par-1 phenotype. These two kinases therefore function in a conserved pathway for axis formation in flies and worms. lkb1 mutant clones also disrupt apical–basal epithelial polarity, suggesting a general role in cell polarization. The human homologue, LKB1, is mutated in Peutz–Jeghers syndrome6,7 and is regulated by prenylation and by phosphorylation by protein kinase A8,9. We show that protein kinase A phosphorylates Drosophila LKB1 on a conserved site that is important for its activity. Thus, Drosophila and human LKB1 may be functional homologues, suggesting that loss of cell polarity may contribute to tumour formation in individuals with Peutz–Jeghers syndrome.

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Figure 1: lkb1 mutants affect oocyte polarity.
Figure 2: Conservation and localization of LKB1.
Figure 3: Analysis of LKB1 regulation.
Figure 4: lkb1 is required for epithelial polarity.


  1. Kemphues, K. J., Priess, J. R., Morton, D. G. & Cheng, N. S. Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52, 311–320 (1988)

    CAS  Article  PubMed  Google Scholar 

  2. Watts, J. L., Morton, D. G., Bestman, J. & Kemphues, K. J. The C. elegans par-4 gene encodes a putative serine–threonine kinase required for establishing embryonic asymmetry. Development 127, 1467–1475 (2000)

    CAS  PubMed  Google Scholar 

  3. Guo, S. & Kemphues, K. J. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81, 611–620 (1995)

    CAS  Article  PubMed  Google Scholar 

  4. Shulman, J. M., Benton, R. & St Johnston, D. The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localization to the posterior pole. Cell 101, 377–388 (2000)

    CAS  Article  PubMed  Google Scholar 

  5. Tomancak, P. et al. A Drosophila melanogaster homologue of Caenorhabditis elegans par-1 acts at an early step in embryonic-axis formation. Nature Cell Biol. 2, 458–460 (2000)

    CAS  Article  PubMed  Google Scholar 

  6. Hemminki, A. et al. A serine/threonine kinase gene defective in Peutz–Jeghers syndrome. Nature 391, 184–187 (1998)

    ADS  CAS  Article  PubMed  Google Scholar 

  7. Jenne, D. E. et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nature Genet. 18, 38–43 (1998)

    CAS  Article  PubMed  Google Scholar 

  8. Collins, S. P., Reoma, J. L., Gamm, D. M. & Uhler, M. D. LKB1, a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase (PKA) and prenylated in vivo. Biochem. J. 345, 673–680 (2000)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Sapkota, G. P. et al. Phosphorylation of the protein kinase mutated in Peutz–Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90RSK and cAMP-dependent protein kinase, but not its farnesylation at Cys433, is essential for LKB1 to suppress cell growth. J. Biol. Chem. 276, 19469–19482 (2001)

    CAS  Article  PubMed  Google Scholar 

  10. van Eeden, F. & St Johnston, D. The polarisation of the anterior–posterior and dorsal–ventral axes during Drosophila oogenesis. Curr. Opin. Genet. Dev. 9, 396–404 (1999)

    CAS  Article  PubMed  Google Scholar 

  11. St Johnston, D., Beuchle, D. & Nüsslein-Volhard, C. Staufen, a gene required to localize maternal RNAs in the Drosophila egg. Cell 66, 51–63 (1991)

    CAS  Article  PubMed  Google Scholar 

  12. Clark, I., Giniger, E., Ruohola-Baker, H., Jan, L. Y. & Jan, Y. L. Transient posterior localization of a kinesin fusion protein reflects anteroposterior polarity of the Drosophila oocyte. Curr. Biol. 4, 289–300 (1994)

    CAS  Article  PubMed  Google Scholar 

  13. Martin, S. G., Dobi, K. C. & St Johnston, D. A rapid method to map mutations in Drosophila. Genome Biol. 2, research0036.1–12 (2001)

    Article  Google Scholar 

  14. Benton, R., Palacios, I. M. & St Johnston, D. Drosophila 14–3–3/PAR-5 is an essential mediator of PAR-1 function in axis formation. Dev. Cell 3, 659–671 (2002)

    CAS  Article  PubMed  Google Scholar 

  15. Spradling, A. The Development of Drosophila melanogaster (eds Bate, M. & Martinez-Arias, A.) 1–70 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1993)

    Google Scholar 

  16. Huynh, J. R., Shulman, J. M., Benton, R. & St Johnston, D. PAR-1 is required for the maintenance of oocyte fate in Drosophila. Development 128, 1201–1209 (2001)

    CAS  PubMed  Google Scholar 

  17. Cox, D. N., Lu, B., Sun, T. Q., Williams, L. T. & Jan, Y. N. Drosophila par-1 is required for oocyte differentiation and microtubule organization. Curr. Biol. 11, 75–87 (2001)

    CAS  Article  PubMed  Google Scholar 

  18. de Cuevas, M. & Spradling, A. C. Morphogenesis of the Drosophila fusome and its implications for oocyte specification. Development 125, 2781–2789 (1998)

    CAS  PubMed  Google Scholar 

  19. Rorth, P. Gal4 in the Drosophila female germline. Mech. Dev. 78, 113–118 (1998)

    CAS  Article  PubMed  Google Scholar 

  20. Lane, M. E. & Kalderon, D. RNA localization along the anteroposterior axis of the Drosophila oocyte requires PKA-mediated signal transduction to direct normal microtubule organization. Genes Dev. 8, 2986–2995 (1994)

    CAS  Article  PubMed  Google Scholar 

  21. Hemminki, A. The molecular basis and clinical aspects of Peutz–Jeghers syndrome. Cell. Mol. Life Sci. 55, 735–750 (1999)

    CAS  Article  PubMed  Google Scholar 

  22. Sanchez-Cespedes, M. et al. Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res. 62, 3659–3662 (2002)

    CAS  PubMed  Google Scholar 

  23. Yoo, L. I., Chung, D. C. & Yuan, J. LKB1—a master tumour suppressor of the small intestine and beyond. Nature Rev. Cancer 2, 529–535 (2002)

    CAS  Article  Google Scholar 

  24. Bardeesy, N. et al. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 419, 162–167 (2002)

    ADS  CAS  Article  PubMed  Google Scholar 

  25. Xu, T. & Rubin, G. M. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117, 1223–1237 (1993)

    CAS  PubMed  Google Scholar 

  26. Chou, T. B. & Perrimon, N. The autosomal FLP–DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics 144, 1673–1679 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Sanson, B., White, P. & Vincent, J. P. Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature 383, 627–630 (1996)

    ADS  Article  PubMed  Google Scholar 

  28. Wodarz, A., Hinz, U., Engelbert, M. & Knust, E. Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell 82, 67–76 (1995)

    CAS  Article  PubMed  Google Scholar 

  29. Sun, T. Q. et al. PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Nature Cell Biol. 3, 628–636 (2001)

    CAS  Article  PubMed  Google Scholar 

  30. Theurkauf, W. Drosophila melanogaster: Practical Uses in Cell and Molecular Biology (eds Goldstein, L. & Fyrberg, E.) 489–506 (Academic, London, 1994)

    Google Scholar 

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We thank M. Pal for fly injection; K. Litière for generating the kinesin–β-gal line; I. Palacios, B. Sanson, A. Wodarz and the Developmental Studies Hybridoma Bank for strains and antibodies; and J. Rouse, N. Lowe, J. Raff and R. Benton for advice and discussion. S.G.M. was supported by the Swiss National Science Foundation and D.StJ. by the Wellcome Trust.

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Correspondence to Daniel St Johnston.

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Martin, S., St Johnston, D. A role for Drosophila LKB1 in anterior–posterior axis formation and epithelial polarity. Nature 421, 379–384 (2003).

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