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. 1999 Dec;153(4):1641–1654. doi: 10.1093/genetics/153.4.1641

SEL-5, a serine/threonine kinase that facilitates lin-12 activity in Caenorhabditis elegans.

H Fares 1, I Greenwald 1
PMCID: PMC1460874  PMID: 10581273

Abstract

Ligands present on neighboring cells activate receptors of the LIN-12/Notch family by inducing a proteolytic cleavage event that releases the intracellular domain. Mutations that appear to eliminate sel-5 activity are able to suppress constitutive activity of lin-12(d) mutations that are point mutations in the extracellular domain of LIN-12, but cannot suppress lin-12(intra), the untethered intracellular domain. These results suggest that sel-5 acts prior to or during ligand-dependent release of the intracellular domain. In addition, sel-5 suppression of lin-12(d) mutations is tissue specific: loss of sel-5 activity can suppress defects in the anchor cell/ventral uterine precursor cell fate decision and a sex myoblast/coelomocyte decision, but cannot suppress defects in two different ventral hypodermal cell fate decisions in hermaphrodites and males. sel-5 encodes at least two proteins, from alternatively spliced mRNAs, that share an amino-terminal region and differ in the carboxy-terminal region. The amino-terminal region contains the hallmarks of a serine/threonine kinase domain, which is most similar to mammalian GAK1 and yeast Pak1p.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Baird S. E., Fitch D. H., Kassem I. A., Emmons S. W. Pattern formation in the nematode epidermis: determination of the arrangement of peripheral sense organs in the C. elegans male tail. Development. 1991 Oct;113(2):515–526. doi: 10.1242/dev.113.2.515. [DOI] [PubMed] [Google Scholar]
  3. Barstead R. J., Waterston R. H. The basal component of the nematode dense-body is vinculin. J Biol Chem. 1989 Jun 15;264(17):10177–10185. [PubMed] [Google Scholar]
  4. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chalfie M., Tu Y., Euskirchen G., Ward W. W., Prasher D. C. Green fluorescent protein as a marker for gene expression. Science. 1994 Feb 11;263(5148):802–805. doi: 10.1126/science.8303295. [DOI] [PubMed] [Google Scholar]
  6. Chow K. L., Hall D. H., Emmons S. W. The mab-21 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates. Development. 1995 Nov;121(11):3615–3626. doi: 10.1242/dev.121.11.3615. [DOI] [PubMed] [Google Scholar]
  7. De Strooper B., Annaert W., Cupers P., Saftig P., Craessaerts K., Mumm J. S., Schroeter E. H., Schrijvers V., Wolfe M. S., Ray W. J. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 1999 Apr 8;398(6727):518–522. doi: 10.1038/19083. [DOI] [PubMed] [Google Scholar]
  8. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eastman D. S., Slee R., Skoufos E., Bangalore L., Bray S., Delidakis C. Synergy between suppressor of Hairless and Notch in regulation of Enhancer of split m gamma and m delta expression. Mol Cell Biol. 1997 Sep;17(9):5620–5628. doi: 10.1128/mcb.17.9.5620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fire A. Integrative transformation of Caenorhabditis elegans. EMBO J. 1986 Oct;5(10):2673–2680. doi: 10.1002/j.1460-2075.1986.tb04550.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fitzgerald K., Wilkinson H. A., Greenwald I. glp-1 can substitute for lin-12 in specifying cell fate decisions in Caenorhabditis elegans. Development. 1993 Dec;119(4):1019–1027. doi: 10.1242/dev.119.4.1019. [DOI] [PubMed] [Google Scholar]
  12. Greenwald I. S., Sternberg P. W., Horvitz H. R. The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell. 1983 Sep;34(2):435–444. doi: 10.1016/0092-8674(83)90377-x. [DOI] [PubMed] [Google Scholar]
  13. Greenwald I. LIN-12/Notch signaling: lessons from worms and flies. Genes Dev. 1998 Jun 15;12(12):1751–1762. doi: 10.1101/gad.12.12.1751. [DOI] [PubMed] [Google Scholar]
  14. Greenwald I., Seydoux G. Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans. Nature. 1990 Jul 12;346(6280):197–199. doi: 10.1038/346197a0. [DOI] [PubMed] [Google Scholar]
  15. Han M., Sternberg P. W. Analysis of dominant-negative mutations of the Caenorhabditis elegans let-60 ras gene. Genes Dev. 1991 Dec;5(12A):2188–2198. doi: 10.1101/gad.5.12a.2188. [DOI] [PubMed] [Google Scholar]
  16. Hodgkin J., Papp A., Pulak R., Ambros V., Anderson P. A new kind of informational suppression in the nematode Caenorhabditis elegans. Genetics. 1989 Oct;123(2):301–313. doi: 10.1093/genetics/123.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hubbard E. J., Dong Q., Greenwald I. Evidence for physical and functional association between EMB-5 and LIN-12 in Caenorhabditis elegans. Science. 1996 Jul 5;273(5271):112–115. doi: 10.1126/science.273.5271.112. [DOI] [PubMed] [Google Scholar]
  18. Jarriault S., Brou C., Logeat F., Schroeter E. H., Kopan R., Israel A. Signalling downstream of activated mammalian Notch. Nature. 1995 Sep 28;377(6547):355–358. doi: 10.1038/377355a0. [DOI] [PubMed] [Google Scholar]
  19. Kaltenboeck B., Spatafora J. W., Zhang X., Kousoulas K. G., Blackwell M., Storz J. Efficient production of single-stranded DNA as long as 2 kb for sequencing of PCR-amplified DNA. Biotechniques. 1992 Feb;12(2):164, 166, 168-71. [PubMed] [Google Scholar]
  20. Kimble J., Hirsh D. The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Dev Biol. 1979 Jun;70(2):396–417. doi: 10.1016/0012-1606(79)90035-6. [DOI] [PubMed] [Google Scholar]
  21. Ko L. J., Prives C. p53: puzzle and paradigm. Genes Dev. 1996 May 1;10(9):1054–1072. doi: 10.1101/gad.10.9.1054. [DOI] [PubMed] [Google Scholar]
  22. Kopan R., Nye J. S., Weintraub H. The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD. Development. 1994 Sep;120(9):2385–2396. doi: 10.1242/dev.120.9.2385. [DOI] [PubMed] [Google Scholar]
  23. Kopan R., Schroeter E. H., Weintraub H., Nye J. S. Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1683–1688. doi: 10.1073/pnas.93.4.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Krause M., Hirsh D. A trans-spliced leader sequence on actin mRNA in C. elegans. Cell. 1987 Jun 19;49(6):753–761. doi: 10.1016/0092-8674(87)90613-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Levine A. J. p53, the cellular gatekeeper for growth and division. Cell. 1997 Feb 7;88(3):323–331. doi: 10.1016/s0092-8674(00)81871-1. [DOI] [PubMed] [Google Scholar]
  26. Levitan D., Greenwald I. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature. 1995 Sep 28;377(6547):351–354. doi: 10.1038/377351a0. [DOI] [PubMed] [Google Scholar]
  27. Levitan D., Greenwald I. LIN-12 protein expression and localization during vulval development in C. elegans. Development. 1998 Aug;125(16):3101–3109. doi: 10.1242/dev.125.16.3101. [DOI] [PubMed] [Google Scholar]
  28. Li X., Greenwald I. HOP-1, a Caenorhabditis elegans presenilin, appears to be functionally redundant with SEL-12 presenilin and to facilitate LIN-12 and GLP-1 signaling. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12204–12209. doi: 10.1073/pnas.94.22.12204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lieber T., Kidd S., Alcamo E., Corbin V., Young M. W. Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei. Genes Dev. 1993 Oct;7(10):1949–1965. doi: 10.1101/gad.7.10.1949. [DOI] [PubMed] [Google Scholar]
  30. Logeat F., Bessia C., Brou C., LeBail O., Jarriault S., Seidah N. G., Israël A. The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8108–8112. doi: 10.1073/pnas.95.14.8108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mello C. C., Kramer J. M., Stinchcomb D., Ambros V. Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 1991 Dec;10(12):3959–3970. doi: 10.1002/j.1460-2075.1991.tb04966.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pulak R., Anderson P. mRNA surveillance by the Caenorhabditis elegans smg genes. Genes Dev. 1993 Oct;7(10):1885–1897. doi: 10.1101/gad.7.10.1885. [DOI] [PubMed] [Google Scholar]
  33. Rooke J., Pan D., Xu T., Rubin G. M. KUZ, a conserved metalloprotease-disintegrin protein with two roles in Drosophila neurogenesis. Science. 1996 Aug 30;273(5279):1227–1231. doi: 10.1126/science.273.5279.1227. [DOI] [PubMed] [Google Scholar]
  34. Rosenbluth R. E., Cuddeford C., Baillie D. L. Mutagenesis in Caenorhabditis elegans. II. A spectrum of mutational events induced with 1500 r of gamma-radiation. Genetics. 1985 Mar;109(3):493–511. doi: 10.1093/genetics/109.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schroeter E. H., Kisslinger J. A., Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature. 1998 May 28;393(6683):382–386. doi: 10.1038/30756. [DOI] [PubMed] [Google Scholar]
  36. Sedensky M. M., Meneely P. M. Genetic analysis of halothane sensitivity in Caenorhabditis elegans. Science. 1987 May 22;236(4804):952–954. doi: 10.1126/science.3576211. [DOI] [PubMed] [Google Scholar]
  37. Selkoe D. J. The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease. Trends Cell Biol. 1998 Nov;8(11):447–453. doi: 10.1016/s0962-8924(98)01363-4. [DOI] [PubMed] [Google Scholar]
  38. Seydoux G., Greenwald I. Cell autonomy of lin-12 function in a cell fate decision in C. elegans. Cell. 1989 Jun 30;57(7):1237–1245. doi: 10.1016/0092-8674(89)90060-3. [DOI] [PubMed] [Google Scholar]
  39. Stewart H. I., O'Neil N. J., Janke D. L., Franz N. W., Chamberlin H. M., Howell A. M., Gilchrist E. J., Ha T. T., Kuervers L. M., Vatcher G. P. Lethal mutations defining 112 complementation groups in a 4.5 Mb sequenced region of Caenorhabditis elegans chromosome III. Mol Gen Genet. 1998 Nov;260(2-3):280–288. doi: 10.1007/pl00013816. [DOI] [PubMed] [Google Scholar]
  40. Struhl G., Greenwald I. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature. 1999 Apr 8;398(6727):522–525. doi: 10.1038/19091. [DOI] [PubMed] [Google Scholar]
  41. Tax F. E., Thomas J. H., Ferguson E. L., Horvitz H. R. Identification and characterization of genes that interact with lin-12 in Caenorhabditis elegans. Genetics. 1997 Dec;147(4):1675–1695. doi: 10.1093/genetics/147.4.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tax F. E., Yeargers J. J., Thomas J. H. Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila. Nature. 1994 Mar 10;368(6467):150–154. doi: 10.1038/368150a0. [DOI] [PubMed] [Google Scholar]
  43. Thiagalingam S., Kinzler K. W., Vogelstein B. PAK1, a gene that can regulate p53 activity in yeast. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6062–6066. doi: 10.1073/pnas.92.13.6062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wen C., Metzstein M. M., Greenwald I. SUP-17, a Caenorhabditis elegans ADAM protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling. Development. 1997 Dec;124(23):4759–4767. doi: 10.1242/dev.124.23.4759. [DOI] [PubMed] [Google Scholar]
  45. Wilkinson H. A., Fitzgerald K., Greenwald I. Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to commitment in a C. elegans cell fate decision. Cell. 1994 Dec 30;79(7):1187–1198. doi: 10.1016/0092-8674(94)90010-8. [DOI] [PubMed] [Google Scholar]
  46. Yochem J., Greenwald I. glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins. Cell. 1989 Aug 11;58(3):553–563. doi: 10.1016/0092-8674(89)90436-4. [DOI] [PubMed] [Google Scholar]

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