The Caenorhabditis elegans Locus lin-15, a Negative Regulator of a Tyrosine Kinase Signaling Pathway, Encodes Two Different Proteins

INVESTIGATIONS

The Caenorhabditis elegans Locus lin-15, a Negative Regulator of a Tyrosine Kinase Signaling Pathway, Encodes Two Different Proteins

S. G. Clark, X. Lu and H. R. Horvitz
Current address: Department of Anatomy, University of California, San Francisco, California 94143.

The Caenorhabditis elegans locus lin-15 negatively regulates an intercellular signaling process that induces formation of the hermaphrodite vulva. The lin-15 locus controls two separate genetic activities. Mutants that lack both activities have multiple, ectopic pseudo-vulvae resulting from the overproduction of vulval cells, whereas mutants defective in only one lin-15 activity appear wild-type. lin-15 acts non-cell-autonomously to prevent the activation of a receptor tyrosine kinase/ras signaling pathway. We report here the molecular characterization of the lin-15 locus. The two lin-15 activities are encoded by contiguous genomic regions and by two distinct, non-overlapping transcripts that may be processed from a single mRNA precursor by trans-splicing. Based on the DNA sequence, the 719- and 1,440-amino acid lin-15 proteins are not similar to each other or to known proteins. lin-15 multivulva mutants, which are defective in both lin-15 activities, contain deletions and insertions that affect the lin-15 genomic region.

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				Y. Xue, H. Fares, B. Grant, Z. Li, A. M. Rose, S. G. Clark, and E. Y. Skolnik Genetic Analysis of the Myotubularin Family of Phosphatases in Caenorhabditis elegans J. Biol. Chem., September 5, 2003; 278(36): 34380 - 34386. [Abstract] [Full Text] [PDF]

				M. Thellmann, J. Hatzold, and B. Conradt The Snail-like CES-1 protein of C. elegans can block the expression of theBH3-only cell-death activator gene egl-1 by antagonizing the function of bHLH proteins Development, September 1, 2003; 130(17): 4057 - 4071. [Abstract] [Full Text] [PDF]

				S. G. Clark and C. Chiu C. elegans ZAG-1, a Zn-finger-homeodomain protein, regulates axonal development and neuronal differentiation Development, August 15, 2003; 130(16): 3781 - 3794. [Abstract] [Full Text] [PDF]

				D. S. Fay, E. Large, M. Han, and M. Darland lin-35/Rb and ubc-18, an E2 ubiquitin-conjugating enzyme, function redundantly to control pharyngeal morphogenesis in C. elegans Development, July 15, 2003; 130(14): 3319 - 3330. [Abstract] [Full Text] [PDF]

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				S. Shaham and C. I. Bargmann Control of neuronal subtype identity by the C. elegans ARID protein CFI-1 Genes & Dev., April 15, 2002; 16(8): 972 - 983. [Abstract] [Full Text] [PDF]

				D. S. Fay, S. Keenan, and M. Han fzr-1 and lin-35/Rb function redundantly to control cell proliferation in C. elegans as revealed by a nonbiased synthetic screen Genes & Dev., February 15, 2002; 16(4): 503 - 517. [Abstract] [Full Text] [PDF]

				V. Hsu, C. L. Zobel, E. J. Lambie, T. Schedl, and K. Kornfeld Caenorhabditis elegans lin-45 raf Is Essential for Larval Viability, Fertility and the Induction of Vulval Cell Fates Genetics, February 1, 2002; 160(2): 481 - 492. [Abstract] [Full Text] [PDF]

				Z. Chen and M. Han Role of C. elegans lin-40 MTA in vulval fate specification and morphogenesis Development, December 1, 2001; 128(23): 4911 - 4921. [Abstract] [Full Text] [PDF]

				E. A. Lundquist, P. W. Reddien, E. Hartwieg, H. R. Horvitz, and C. I. Bargmann Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis Development, November 15, 2001; 128(22): 4475 - 4488. [Abstract] [Full Text] [PDF]

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