C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation
NaturePublished 1 May 1993
Min Han, Andy Golden, Yu-ming Han, Paul W. Sternberg
Citations276
SJR quartileQ1
SJR score18.29
SNIP10.16
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The lin-45 raf gene product appears to act downstream of the ras protein in this pathway, suggesting a proto-oncogene-mediated signalling pathway may be a common feature of metazoan development.
Abstract
Vulval differentiation in Caenorhabditis elegans is controlled by intercellular signalling mediated by a receptor tyrosine kinase and a ras gene product. The lin-45 gene encodes a homologue of the raf family of serine/threonine kinases and is necessary for vulval differentiation. The lin-45 raf gene product appears to act downstream of the ras protein in this pathway. A proto-oncogene-mediated signalling pathway may be a common feature of metazoan development.
Keywords
MedicineNeuroscienceBiochemistry, Genetics and Molecular Biology
Molecular Cloning: A Laboratory Manual 2
129,982 Citations1989Joseph Sambrook, Elisabeth Fritsch +1 more
The content has been entirely recast to include nucleic-acid based methods selected as the most widely used and valuable in molecular and cellular biology laboratories.
GeneticsTHE GENETICS OF <i>CAENORHABDITIS ELEGANS</i>
15,460 Citations1974Sydney Brenner
Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C. elegans are large.
Proceedings of the National Academy of SciencesRapid and efficient site-specific mutagenesis without phenotypic selection.
7,325 Citations1985Thomas A. Kunkel
The high efficiency, approximately equal to 10-fold greater than that observed using current methods without enrichment procedures, is obtained by using a DNA template containing several uracil residues in place of thymine, which is applied to mutations introduced via both oligonucleotides and error-prone polymerization.
Developmental BiologyPost-embryonic cell lineages of the nematode, Caenorhabditis elegans
3,584 Citations1977J.E. Sulston, H. Robert Horvitz
These cell lineages range in length from one to eight sequential divisions and lead to significant developmental changes in the neuronal, muscular, hypodermal, and digestive systems and are determined by direct observation of the divisions, migrations, and deaths of individual cells in living nematodes.
The Journal of Cell BiologyThe scanning model for translation: an update.
3,535 Citations1989M Kozak
The small (40S) subunit of eukaryotic ribosomes is believed to bind initially at the capped 5'-end of messenger RNA and then migrate, stopping at the first AUG codon in a favorable context for initiating translation.
The EMBO JournalEfficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences.
3,219 Citations1991C C Mello, James M. Kramer +2 more
A dominant behavioral marker, rol‐6(su‐1006), and an efficient microinjection procedure which facilitate the recovery of Caenorhabditis elegans transformants are described and it is shown that low copy number extrachromosomal transformation can be achieved by adjusting the relative concentration of DNA molecules in the injection mixture.
Cold Spring Harbor Laboratory eBooksThe Nematode Caenorhabditis elegans
2,841 Citations1988William B. Wood
This "Book of the Worm" serves as a reference source for C. elegans investigators as well as an introductory monograph for other biologists.
CellThe SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling
1,653 Citations1992Eve J. Lowenstein, Roger J. Daly +8 more
Results suggest that GRB2/sem-5 plays a crucial role in a highly conserved mechanism for growth factor control of ras signaling.
Developmental BiologyThe postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans
885 Citations1979Judith Kimble, David Hirsh
Variation in the hermaphrodite lineage suggests that cell-cell interaction may play a more significant role in organisms that develop by invariant lineages than has hitherto been considered.
CellA trans-spliced leader sequence on actin mRNA in C. elegans
636 Citations1987Michael Krause, David Hirsh
The evidence suggests that the actin mRNA leader sequence is acquired from this novel nucleotide transcript by an intermolecular trans-splicing mechanism.
Proceedings of the National Academy of SciencesToward a physical map of the genome of the nematode <i>Caenorhabditis elegans</i>
630 Citations1986Alan Coulson, John Sulston +2 more
A technique for digital characterization and comparison of DNA fragments, using restriction enzymes, is described, being applied to fragments from the nematode Caenorhabditis elegans to facilitate cross-indexing of clones emanating from different laboratories and to construct a physical map of the genome.
NatureC. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains
602 Citations1992Scott G. Clark, Michael Stern +1 more
The results indicate that the sem-5 gene encodes a novel protein that functions in at least two distinct cell-signalling processes, both in vulval induction and in sex myoblast migration.
GeneticsIDENTIFICATION AND CHARACTERIZATION OF 22 GENES THAT AFFECT THE VULVAL CELL LINEAGES OF THE NEMATODE <i>CAENORHABDITIS ELEGANS</i>
543 Citations1985Edwin L. Ferguson, H. Robert Horvitz
The results suggest that most, or all, genes of the Vulvaless or Multivulva classes may have been identified; the absence of the activity of any of these genes probably results in lethality or sterility.
NatureRaf-1 protein kinase is required for growth of induced NIH/3T3 cells
484 Citations1991Walter Kölch, Gisela Heidecker +2 more
It is concluded that raf functions as an essential signal transducer downstream of serum growth factor receptors, protein kinase C and ras to determine whether Raf-1 is essential for receptor signalling.
Genes & DevelopmentSerum-, TPA-, and Ras-induced expression from Ap-1/Ets-driven promoters requires Raf-1 kinase.
451 Citations1992Joseph T. Bruder, Gisela Heidecker +1 more
It is shown that Raf-1 and Ras cooperate in trans-activation through the oncogene-responsive element and that the cysteine-rich region is necessary for this effect.
Proceedings of the National Academy of SciencesPhorbol ester binding to protein kinase C requires a cysteine-rich zinc-finger-like sequence.
440 Citations1989Yoshitaka Ono, Tomoko Fujii +5 more
Radioactive phorbol 12,13-dibutyrate binding analysis indicated that a cysteine-rich zinc-finger-like sequence was essential for protein kinase C to bind phorbobol ester and that one of two sequences was sufficient for the phorbl ester binding.
NatureGenome linking with yeast artificial chromosomes
435 Citations1988Alan Coulson, R Waterston +3 more
The technique involves the ligation of large genomic fragments into a vector that provides centromeric, telomeric and selective functions; the constructs are then introduced into Saccharomyces cerevisiae, and replicate in the same manner as the host chromosomes.
NatureThe let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily
422 Citations1990Raffi V. Aroian, Makoto Koga +3 more
The identification of the let-23 product provides support for a link in vivo between tyrosine kinase growth factor receptors and ras proteins in a pathway of cell-type determination.
GeneticsISOLATION AND GENETIC CHARACTERIZATION OF CELL-LINEAGE MUTANTS OF THE NEMATODE <i>CAENORHABDITIS ELEGANS</i>
420 Citations1980H. Robert Horvitz, John Sulston
Twenty-four mutants that alter the normally invariant post-embryonic cell lineages of the nematode Caenorhabditis elegans have been isolated and genetically characterized, suggesting that their phenotypes result from the complete absence of gene activity.
NatureCaenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction
418 Citations1990Greg J. Beitel, Scott G. Clark +1 more
The let-60 gene, an essential ras gene of the nematode Caenorhabditis elegans, acts as a switch in the inductive signalling pathway that initiates vulva formation, and other genes within this pathway seem likely to encode molecules that regulateLet-60 function as well as molecules that are targets of let- 60 action.
Celllet-60, a gene that specifies cell fates during C. elegans vulval induction, encodes a ras protein
400 Citations1990Min Han, Paul W. Sternberg
Cloned the let-60 gene is cloned, and it is shown that it encodes a gene product identical in 84% of its first 164 amino acids to ras gene products from other vertebrate and invertebrate species, suggesting that theLet-60 product contains all the biochemical functions of ras proteins.
NatureThe gene lin-3 encodes an inductive signal for vulval development in C. elegans
397 Citations1992Russell J. Hill, Paul W. Sternberg
The lin-3 gene is necessary for induction of the Caenorhabditis elegans vulva by the anchor cell and encodes a molecule similar to epidermal growth factor and to transforming growth factor-a and acts through the epider mal growth factor receptor homologue let-23.
NatureA genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans
333 Citations1987Edwin L. Ferguson, Paul W. Sternberg +1 more
Twenty-three genes have been assigned to particular steps in a genetic pathway for the specification of the vulval cell lineages of the nematode Caenorhabditis elegans, suggesting that these lineages may be specified by a series of decisions that distinguish between alternative cell fates.
NatureRaf functions downstream of Rasl in the Sevenless signal transduction pathway
316 Citations1992Barry J. Dickson, Frank Sprenger +2 more
It is shown that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function.
CellA cell that dies during wild-type C. elegans development can function as a neuron in a ced-3 mutant
282 Citations1987Leon Avery, H. Robert Horvitz
It is shown that the pharyngeal neuron M4 is essential for feeding in wild-type worms, but in a ced-3 mutant, one of the extra cells, probably MSpaaaaap (the sister of M4), can sometimes take over M4's function.
Developmental BiologyAbnormal cell lineages in mutants of the nematode Caenorhabditis elegans
274 Citations1981John Sulston, H. Robert Horvitz
The phenotypes of cell lineage mutants of the nematode Caenorhabditis elegans are described, which define 14 genes, which differ in the breadth and nature of their phenotypic defects.
Journal of Biological ChemistryThe basal component of the nematode dense-body is vinculin
252 Citations1989Robert Barstead, R Waterston
The complete sequence of the deb-1 gene, its localization on the C. elegans genetic map, and the finding that it encodes a protein with a sequence very similar to chicken vinculin are reported.
CellThe combined action of two intercellular signaling pathways specifies three cell fates during vulval induction in C. elegans
246 Citations1989Paul W. Sternberg, H. Robert Horvitz
A model for the regulatory circuitry underlying VPC determination that includes a role for lin-12 in both autocrine and paracrine VPC signaling is described, suggesting that specification of the three VPC fates is accomplished by two binary decisions, each effected by one of the two signaling pathways.
NatureMultiple intercellular signalling systems control the development of the Caenorhabditis elegans vulva
246 Citations1991H. Robert Horvitz, Paul W. Sternberg
The biology of vulval development provides a framework for understanding how cell interactions control the development of animals as diverse as nematodes, insects and mammals.
Nucleic Acids ResearchThe complete coding sequence of the human raf oncogene and the corresponding structure of the c-raf-1 gene
222 Citations1986Tom I. Bonner, Herman Oppermann +5 more
The complete 648 amino acid sequence of the human raf oncogene was deduced from the 2977 nucleotide sequence of a fetal liver cDNA to obtain clones which extend the human c-raf-1 locus by an additional 18.9 kb at the 5' end and contain all the remaining coding exons.
GeneticsMUTATIONS WITH DOMINANT EFFECTS ON THE BEHAVIOR AND MORPHOLOGY OF THE NEMATODE <i>CAENORHABDITIS ELEGANS</i>
199 Citations1986Eun-Chung Park, H. Robert Horvitz
Thirty mutations that have dominant effects on the behavior or morphology of the nematode Caenorhabditis elegans are analyzed and 15 genes appear to define 15 genes, which are led to two notable conclusions.
NatureLimitation of the size of the vulval primordium of Caenorhabditis elegans by lin-15 expression in surrounding hypodermis
196 Citations1990Robert K Herman, Edward M. Hedgecock
It is demonstrated here that lin-15(+) expression is necessary in cells other than the vulval precursor cells or the anchor cell, most probably in the hyp7 syncytium, and proposed that lin+ is active in hyp7 in order to repress an intrinsic vulval program in the precursor cells.
ScienceIdentification and Characterization of Zinc Binding Sites in Protein Kinase C
196 Citations1991Stevan R. Hubbard, W. Robert Bishop +4 more
Direct evidence has been obtained that PKC beta I tightly binds four zinc ions per molecule and extended x-ray absorption fine structure (EXAFS) data are best fit by an average Zn2+ coordination of one nitrogen and three sulfur atoms.
GeneticsThe let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans.
195 Citations1990May Han, Raffi V. Aroian +1 more
The genetic interaction studies suggest that let-60 acts downstream of let-23 and lin-15 and upstream of lin-1 and lin -12 in the genetic pathway specifying the switch between vulval and nonvulval cell types.
GeneticsMultiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction.
172 Citations1991Raffi V. Aroian, Paul W. Sternberg
It is shown that let-23 function is required for vulval precursor cells (VPCs) to respond to the signal that induces vulval differentiation, and analysis of 16 newLet-23 mutations indicates that the let-21 receptor tyrosine kinase functions in at least five tissues.
Molecular and Cellular BiologyNeither arginine nor histidine can carry out the function of lysine-295 in the ATP-binding site of p60src.
156 Citations1986Mark P. Kamps, Bartholomew M. Sefton
Current Opinion in Structural BiologyEukaryotic protein kinases
137 Citations1991Steven K. Hanks
A classification scheme based on catalytic-domain sequence similarities groups together protein kinases that have similar overall structures, modes of regulation, and catalytic properties.
Advances in cancer researchThe Role of Raf-1 Phosphorylation in Signal Transduction
134 Citations1992Gisela Heidecker, Walter Kölch +2 more
Raf-1 has a central role in the signal transduction pathways of all growth factors and several immediate early genes are regulated by signals transmitted through Raf- 1; eventually the signaling cascade converge in the activation of the cdc2 complex possibly by inducing one of the cell cycle-specific cyclins.
GeneticsCROSSOVER SUPPRESSORS AND BALANCED RECESSIVE LETHALS IN <i>CAENORHABDITIS ELEGANS</i>
133 Citations1978Robert K Herman
Two dominant suppressors of crossing over have been identified following X-ray treatment of the small nematode C. elegans and are both tightly linked to LGII markers.
Cold Spring Harbor Symposia on Quantitative Biologyraf Family Serine/Threonine Protein Kinases in Mitogen Signal Transduction
120 Citations1988Ulf R. Rapp, Gisela Heidecker +6 more
Genes & DevelopmentAnalysis of dominant-negative mutations of the Caenorhabditis elegans let-60 ras gene.
99 Citations1991May Han, Paul W. Sternberg
Four let-60(dn) mutant genes were introduced into wild-type animals in the form of extrachromosomal arrays and were found to generate three dominant phenotypes--lethality, vulva-less, or multivulva--depending on gene dose and alleles.
GeneticsThe unc-22(IV) region of Caenorhabditis elegans: genetic analysis of lethal mutations.
93 Citations1988Denise V. Clark, T M Rogalski +2 more
A minimum estimate of approximately 3500 essential genes in the Caenorhabditis elegans genome is indicated using the balancer nT1 (IV;V), which suppresses recombination over 49 map units.
Molecular and Cellular BiologySplicing in Caenorhabditis elegans does not require an AG at the 3' splice acceptor site.
70 Citations1993Raffi V. Aroian, Antonin Lévy +4 more
Molecular and Cellular BiologyBiochemical Analysis of Torso and D-Raf During Drosophila Embryogenesis: Implications for Terminal Signal Transduction
48 Citations1993Frank Sprenger, Melissa M. Trosclair +1 more
This report provides the first biochemical analysis of the terminal signal transduction pathway in Drosophila embryos, demonstrating that Torso has intrinsic tyrosine kinase activity and that it is transiently tyosine phosphorylated (activated) at syncytial blastoderm stages.
Molecular and Cellular BiologyBiochemical analysis of torso and D-raf during Drosophila embryogenesis: implications for terminal signal transduction.
36 Citations1993F Sprenger, Melissa M. Trosclair +1 more
Journal of Experimental ZoologyTemperature‐sensitive mutations causing reversible paralysis in <i>Caenorhabditis elegans</i>
19 Citations1985Ryuji Hosono, Sigeru Kuno +1 more
A method has been developed for the isolation of temperature-dependent paralytic mutants of the nematode Caenorhabditis elegans, based on a screening procedure using short-time exposure to 30 degrees C, and one mutation, designated mah-2, is a sex-linked semidominant that is mapped as 0.6 map units left of dpy-6.