Development, Vol 127, Issue 7 1467-1475, Copyright © 2000 by Company of Biologists

JOURNAL ARTICLES

The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry

JL Watts, DG Morton, J Bestman and KJ Kemphues
Section of Genetics and Development, Cornell University, Ithaca, New York 14853, USA.

During the first cell cycle of Caenorhabditis elegans embryogenesis, asymmetries are established that are essential for determining the subsequent developmental fates of the daughter cells. The maternally expressed par genes are required for establishing this polarity. The products of several of the par genes have been found to be themselves asymmetrically distributed in the first cell cycle. We have identified the par-4 gene of C. elegans, and find that it encodes a putative serine-threonine kinase with similarity to a human kinase associated with Peutz-Jeghers Syndrome, LKB1 (STK11), and a Xenopus egg and embryo kinase, XEEK1. Several strong par-4 mutant alleles are missense mutations that alter conserved residues within the kinase domain, suggesting that kinase activity is essential for PAR-4 function. We find that the PAR-4 protein is present in the gonads, oocytes and early embryos of C. elegans, and is both cytoplasmically and cortically distributed. The cortical distribution begins at the late 1-cell stage, is more pronounced at the 2- and 4-cell stages and is reduced at late stages of embryonic development. We find no asymmetry in the distribution of PAR-4 protein in C. elegans embryos. The distribution of PAR-4 protein in early embryos is unaffected by mutations in the other par genes.

This article has been cited by other articles:

				H. Zhang, J. M. Squirrell, and J. G. White RAB-11 Permissively Regulates Spindle Alignment by Modulating Metaphase Microtubule Dynamics in Caenorhabditis elegans Early Embryos Mol. Biol. Cell, June 1, 2008; 19(6): 2553 - 2565. [Abstract] [Full Text] [PDF]

				H. Lee, J. S. Cho, N. Lambacher, J. Lee, S.-J. Lee, T. H. Lee, A. Gartner, and H.-S. Koo The Caenorhabditis elegans AMP-activated Protein Kinase AAK-2 Is Phosphorylated by LKB1 and Is Required for Resistance to Oxidative Stress and for Normal Motility and Foraging Behavior J. Biol. Chem., May 30, 2008; 283(22): 14988 - 14993. [Abstract] [Full Text] [PDF]

				A. F. Hezel, S. Gurumurthy, Z. Granot, A. Swisa, G. C. Chu, G. Bailey, Y. Dor, N. Bardeesy, and R. A. DePinho Pancreatic Lkb1 Deletion Leads to Acinar Polarity Defects and Cystic Neoplasms Mol. Cell. Biol., April 1, 2008; 28(7): 2414 - 2425. [Abstract] [Full Text] [PDF]

				Y. Budirahardja and P. Gonczy PLK-1 asymmetry contributes to asynchronous cell division of C. elegans embryos Development, April 1, 2008; 135(7): 1303 - 1313. [Abstract] [Full Text] [PDF]

				D. M. Rivers, S. Moreno, M. Abraham, and J. Ahringer PAR proteins direct asymmetry of the cell cycle regulators Polo-like kinase and Cdc25 J. Cell Biol., March 5, 2008; 180(5): 877 - 885. [Abstract] [Full Text] [PDF]

				E. G. Beale 5'-AMP-Activated Protein Kinase Signaling in Caenorhabditis elegans Experimental Biology and Medicine, January 1, 2008; 233(1): 12 - 20. [Abstract] [Full Text] [PDF]

				J.-C. Wu and L. S. Rose PAR-3 and PAR-1 Inhibit LET-99 Localization to Generate a Cortical Band Important for Spindle Positioning in Caenorhabditis elegans Embryos Mol. Biol. Cell, November 1, 2007; 18(11): 4470 - 4482. [Abstract] [Full Text] [PDF]

				C. Forcet and M. Billaud Dialogue Between LKB1 and AMPK: A Hot Topic at the Cellular Pole Sci. Signal., September 18, 2007; 2007(404): pe51 - pe51. [Abstract] [Full Text] [PDF]

				S. Bonaccorsi, V. Mottier, M. G. Giansanti, B. J. Bolkan, B. Williams, M. L. Goldberg, and M. Gatti The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division Development, June 1, 2007; 134(11): 2183 - 2193. [Abstract] [Full Text] [PDF]

				B. Zheng and L. C. Cantley Regulation of epithelial tight junction assembly and disassembly by AMP-activated protein kinase PNAS, January 16, 2007; 104(3): 819 - 822. [Abstract] [Full Text] [PDF]

				H.-J. Koh, D. E. Arnolds, N. Fujii, T. T. Tran, M. J. Rogers, N. Jessen, Y. Li, C. W. Liew, R. C. Ho, M. F. Hirshman, et al. Skeletal Muscle-Selective Knockout of LKB1 Increases Insulin Sensitivity, Improves Glucose Homeostasis, and Decreases TRB3 Mol. Cell. Biol., November 15, 2006; 26(22): 8217 - 8227. [Abstract] [Full Text] [PDF]

				L. Zhang, J. Li, L. H. Young, and M. J. Caplan AMP-activated protein kinase regulates the assembly of epithelial tight junctions PNAS, November 14, 2006; 103(46): 17272 - 17277. [Abstract] [Full Text] [PDF]

				M. Beers and K. Kemphues Depletion of the co-chaperone CDC-37 reveals two modes of PAR-6 cortical association in C. elegans embryos Development, October 1, 2006; 133(19): 3745 - 3754. [Abstract] [Full Text] [PDF]

				A. Suzuki and S. Ohno The PAR-aPKC system: lessons in polarity. J. Cell Sci., March 15, 2006; 119(Pt 6): 979 - 987. [Abstract] [Full Text] [PDF]

				P. Narbonne and R. Roy Inhibition of germline proliferation during C. elegans dauer development requires PTEN, LKB1 and AMPK signalling Development, February 15, 2006; 133(4): 611 - 619. [Abstract] [Full Text] [PDF]

				H. Mehenni, N. Lin-Marq, K. Buchet-Poyau, A. Reymond, M. A. Collart, D. Picard, and S. E. Antonarakis LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes Hum. Mol. Genet., August 1, 2005; 14(15): 2209 - 2219. [Abstract] [Full Text] [PDF]

				C. Forcet, S. Etienne-Manneville, H. Gaude, L. Fournier, S. Debilly, M. Salmi, A. Baas, S. Olschwang, H. Clevers, and M. Billaud Functional analysis of Peutz-Jeghers mutations reveals that the LKB1 C-terminal region exerts a crucial role in regulating both the AMPK pathway and the cell polarity Hum. Mol. Genet., May 15, 2005; 14(10): 1283 - 1292. [Abstract] [Full Text] [PDF]

				V Schumacher, T Vogel, B Leube, C Driemel, T Goecke, G Moslein, and B Royer-Pokora STK11 genotyping and cancer risk in Peutz-Jeghers syndrome J. Med. Genet., May 1, 2005; 42(5): 428 - 435. [Full Text] [PDF]

				P A Marignani LKB1, the multitasking tumour suppressor kinase J. Clin. Pathol., January 1, 2005; 58(1): 15 - 19. [Abstract] [Full Text] [PDF]

				J. Boudeau, J. W. Scott, N. Resta, M. Deak, A. Kieloch, D. Komander, D. G. Hardie, A. R. Prescott, D. M. F. van Aalten, and D. R. Alessi Analysis of the LKB1-STRAD-MO25 complex J. Cell Sci., December 15, 2004; 117(26): 6365 - 6375. [Abstract] [Full Text] [PDF]

				J. Apfeld, G. O'Connor, T. McDonagh, P. S. DiStefano, and R. Curtis The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans Genes & Dev., December 15, 2004; 18(24): 3004 - 3009. [Abstract] [Full Text] [PDF]

				R. J. Shaw, M. Kosmatka, N. Bardeesy, R. L. Hurley, L. A. Witters, R. A. DePinho, and L. C. Cantley Inaugural Article: The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress PNAS, March 9, 2004; 101(10): 3329 - 3335. [Abstract] [Full Text] [PDF]

				D. R. Manning Evidence Mounts for Receptor-Independent Activation of Heterotrimeric G Proteins Normally in Vivo: Positioning of the Mitotic Spindle in C. Elegans Sci. Signal., August 19, 2003; 2003(196): pe35 - pe35. [Abstract] [Full Text] [PDF]

				J. B. Blumer, M. L. Bernard, Y. K. Peterson, J.-i. Nezu, P. Chung, D. J. Dunican, J. A. Knoblich, and S. M. Lanier Interaction of Activator of G-protein Signaling 3 (AGS3) with LKB1, a Serine/Threonine Kinase Involved in Cell Polarity and Cell Cycle Progression: PHOSPHORYLATION OF THE G-PROTEIN REGULATORY (GPR) MOTIF AS A REGULATORY MECHANISM FOR THE INTERACTION OF GPR MOTIFS WITH Gi{alpha} J. Biol. Chem., June 20, 2003; 278(26): 23217 - 23220. [Abstract] [Full Text] [PDF]

				J. Pellettieri and G. Seydoux Anterior-Posterior Polarity in C. elegans and Drosophila--PARallels and Differences Science, December 6, 2002; 298(5600): 1946 - 1950. [Abstract] [Full Text] [PDF]

				M. Sanchez-Cespedes, P. Parrella, M. Esteller, S. Nomoto, B. Trink, J. M. Engles, W. H. Westra, J. G. Herman, and D. Sidransky Inactivation of LKB1/STK11 Is a Common Event in Adenocarcinomas of the Lung Cancer Res., July 1, 2002; 62(13): 3659 - 3662. [Abstract] [Full Text] [PDF]

				M. Tiainen, K. Vaahtomeri, A. Ylikorkala, and T. P. Makela Growth arrest by the LKB1 tumor suppressor: induction of p21WAF1/CIP1 Hum. Mol. Genet., June 15, 2002; 11(13): 1497 - 1504. [Abstract] [Full Text] [PDF]

				M.-F. B. Tsou, A. Hayashi, L. R. DeBella, G. McGrath, and L. S. Rose LET-99 determines spindle position and is asymmetrically enriched in response to PAR polarity cues in C. elegans embryos Development, January 10, 2002; 129(19): 4469 - 4481. [Abstract] [Full Text] [PDF]

				N. N. Huang, D. E. Mootz, A. J. M. Walhout, M. Vidal, and C. P. Hunter MEX-3 interacting proteins link cell polarity to asymmetric gene expression in Caenorhabditis elegans Development, January 2, 2002; 129(3): 747 - 759. [Abstract] [Full Text] [PDF]

				M Nakaya, A Fukui, Y Izumi, K Akimoto, M Asashima, and S Ohno Meiotic maturation induces animal-vegetal asymmetric distribution of aPKC and ASIP/PAR-3 in Xenopus oocytes Development, January 12, 2000; 127(23): 5021 - 5031. [Abstract] [PDF]

				P. A. Marignani, F. Kanai, and C. L. Carpenter LKB1 Associates with Brg1 and Is Necessary for Brg1-induced Growth Arrest J. Biol. Chem., August 24, 2001; 276(35): 32415 - 32418. [Abstract] [Full Text] [PDF]

				G. P. Sapkota, A. Kieloch, J. M. Lizcano, S. Lain, J. S. C. Arthur, M. R. Williams, N. Morrice, M. Deak, and D. R. Alessi 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., May 25, 2001; 276(22): 19469 - 19482. [Abstract] [Full Text] [PDF]