Short-range positional signals in the developing Drosophila eye

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 59-63
Author(s):  
Andrew Tomlinson
Keyword(s):  
Transcription Factor ◽  
Tyrosine Kinase ◽  
Gene Product ◽  
Short Range ◽  
Gene Products ◽  
Molecular Approach ◽  
Drosophila Eye

Positional signals provided by immediate neighbours appear to direct developmental decisions in the eye of Drosophila. By a combined genetic and molecular approach the biochemical bases of the signal and reception mechanisms are being systematically dissected. Three key gene products have now been identified, sevenless is a transmembrane tyrosine kinase probably transducing positional signals that direct the R7 cell to its fate. The bride of sevenless gene product is on the signalling side of the mechanism and is required in R8 for R7 to develop. The type of protein bride of sevenless encodes is not yet known. The rough gene encodes a transcription factor on the signalling side required in R2 and R5 for positional signals to be transmitted to neighbouring cells.

Progression of the morphogenetic furrow in the Drosophila eye: the roles of Hedgehog, Decapentaplegic and the Raf pathway

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5795-5808 ◽  
Author(s):  
S. Greenwood ◽  
G. Struhl
Keyword(s):  
Transcription Factor ◽  
Short Range ◽  
Morphogenetic Furrow ◽  
Serine Threonine Kinase ◽  
Present Evidence ◽  
Threonine Kinase ◽  
Drosophila Eye ◽  
Undifferentiated Cells ◽  
Hh Signaling ◽  
Necessary And Sufficient

During Drosophila eye development, Hedgehog (Hh) protein secreted by maturing photoreceptors directs a wave of differentiation that sweeps anteriorly across the retinal primordium. The crest of this wave is marked by the morphogenetic furrow, a visible indentation that demarcates the boundary between developing photoreceptors located posteriorly and undifferentiated cells located anteriorly. Here, we present evidence that Hh controls progression of the furrow by inducing the expression of two downstream signals. The first signal, Decapentaplegic (Dpp), acts at long range on undifferentiated cells anterior to the furrow, causing them to enter a ‘pre-proneural’ state marked by upregulated expression of the transcription factor Hairy. Acquisition of the pre-proneural state appears essential for all prospective retinal cells to enter the proneural pathway and differentiate as photoreceptors. The second signal, presently unknown, acts at short range and is transduced via activation of the Serine-Threonine kinase Raf. Activation of Raf is both necessary and sufficient to cause pre-proneural cells to become proneural, a transition marked by downregulation of Hairy and upregulation of the proneural activator, Atonal (Ato), which initiates differentiation of the R8 photoreceptor. The R8 photoreceptor then organizes the recruitment of the remaining photoreceptors (R1-R7) through additional rounds of Raf activation in neighboring pre-proneural cells. Finally, we show that Dpp signaling is not essential for establishing either the pre-proneural or proneural states, or for progression of the furrow. Instead, Dpp signaling appears to increase the rate of furrow progression by accelerating the transition to the pre-proneural state. In the abnormal situation in which Dpp signaling is blocked, Hh signaling can induce undifferentiated cells to become pre-proneural but does so less efficiently than Dpp, resulting in a retarded rate of furrow progression and the formation of a rudimentary eye.

scholarly journals Deletions within the amino-terminal half of the c-src gene product that alter the functional activity of the protein.

1989 ◽  
Vol 9 (3) ◽  
pp. 1109-1119 ◽  
Author(s):  
S P Nemeth ◽  
L G Fox ◽  
M DeMarco ◽  
J S Brugge
Keyword(s):  
Amino Acids ◽  
Tyrosine Kinase ◽  
Gene Product ◽  
Kinase Activity ◽  
Soft Agar ◽  
Gene Products ◽  
Tyrosine Kinase Activity ◽  
Amino Terminal ◽  
Src Gene

To examine how amino acid sequences outside of the catalytic domain of pp60c-src influence the functional activity of this protein, we have introduced deletion mutations within the amino-terminal half of pp60c-src. These mutations caused distinct changes in the biochemical properties of the c-src gene products and in the properties of cells infected with retroviruses carrying these mutant c-src genes. Cells expressing the c-srcNX protein, which contains a deletion of amino acids 15 to 89, displayed a refractile, spindle-shaped morphology, formed intermediate-sized, tightly packed colonies in soft agar, and contained elevated levels of cellular phosphotyrosine-containing proteins. Thus, deletion of amino acids 15 to 89 can activate the kinase activity and transforming potential of the c-src gene product. Deletion of amino acids 112 to 225, however, did not increase the kinase activity or transforming ability of pp60c-src; indeed, deletion of these sequences in c-srcHP suppressed phenotypic alterations induced by pp60c-src. Cells expressing the c-srcNP or c-srcBS gene products (containing deletions of amino acids 15 to 225 and 55 to 169, respectively) displayed a fusiform, refractile morphology and formed diffuse colonies in soft agar; the mutant proteins displayed an increased in vitro protein-tyrosine kinase activity. However, only a few cellular proteins contained elevated levels of phosphotyrosine in vivo. Thus, deletions downstream of amino acid 89 severely restricted the ability of c-src to phosphorylate cellular substrates in vivo without affecting the intrinsic tyrosine kinase activity of the c-src gene product. These results suggest the existence of at least two modulatory regions within the amino-terminal half of pp60c-src that are important for the regulation of tyrosine kinase activity and for the interaction of pp60c-src with cellular substrates.

Deletions within the amino-terminal half of the c-src gene product that alter the functional activity of the protein

1989 ◽  
Vol 9 (3) ◽  
pp. 1109-1119
Author(s):  
S P Nemeth ◽  
L G Fox ◽  
M DeMarco ◽  
J S Brugge
Keyword(s):  
Amino Acids ◽  
Tyrosine Kinase ◽  
Gene Product ◽  
Kinase Activity ◽  
Soft Agar ◽  
Gene Products ◽  
Tyrosine Kinase Activity ◽  
Amino Terminal ◽  
Src Gene

To examine how amino acid sequences outside of the catalytic domain of pp60c-src influence the functional activity of this protein, we have introduced deletion mutations within the amino-terminal half of pp60c-src. These mutations caused distinct changes in the biochemical properties of the c-src gene products and in the properties of cells infected with retroviruses carrying these mutant c-src genes. Cells expressing the c-srcNX protein, which contains a deletion of amino acids 15 to 89, displayed a refractile, spindle-shaped morphology, formed intermediate-sized, tightly packed colonies in soft agar, and contained elevated levels of cellular phosphotyrosine-containing proteins. Thus, deletion of amino acids 15 to 89 can activate the kinase activity and transforming potential of the c-src gene product. Deletion of amino acids 112 to 225, however, did not increase the kinase activity or transforming ability of pp60c-src; indeed, deletion of these sequences in c-srcHP suppressed phenotypic alterations induced by pp60c-src. Cells expressing the c-srcNP or c-srcBS gene products (containing deletions of amino acids 15 to 225 and 55 to 169, respectively) displayed a fusiform, refractile morphology and formed diffuse colonies in soft agar; the mutant proteins displayed an increased in vitro protein-tyrosine kinase activity. However, only a few cellular proteins contained elevated levels of phosphotyrosine in vivo. Thus, deletions downstream of amino acid 89 severely restricted the ability of c-src to phosphorylate cellular substrates in vivo without affecting the intrinsic tyrosine kinase activity of the c-src gene product. These results suggest the existence of at least two modulatory regions within the amino-terminal half of pp60c-src that are important for the regulation of tyrosine kinase activity and for the interaction of pp60c-src with cellular substrates.

scholarly journals The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a steroid isomerase in Saccharomyces cerevisiae.

1996 ◽  
Vol 16 (6) ◽  
pp. 2719-2727 ◽  
Author(s):  
S Silve ◽  
P Leplatois ◽  
A Josse ◽  
P H Dupuy ◽  
C Lanau ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Proliferation ◽  
Gene Product ◽  
In Vitro Assays ◽  
Gene Products ◽  
Yeast Saccharomyces Cerevisiae ◽  
Isomerase Activity ◽  
Encoding Gene ◽  
Resistant Mutants

SR 31747 is a novel immunosuppressant agent that arrests cell proliferation in the yeast Saccharomyces cerevisiae, SR 31747-treated cells accumulate the same aberrant sterols as those found in a mutant impaired in delta 8- delta 7-sterol isomerase. Sterol isomerase activity is also inhibited by SR 31747 in in vitro assays. Overexpression of the sterol isomerase-encoding gene, ERG2, confers enhanced SR resistance. Cells growing anaerobically on ergosterol-containing medium are not sensitive to SR. Disruption of the sterol isomerase-encoding gene is lethal in cells growing in the absence of exogenous ergosterol, except in SR-resistant mutants lacking either the SUR4 or the FEN1 gene product. The results suggest that sterol isomerase is the target of SR 31747 and that both the SUR4 and FEN1 gene products are required to mediate the proliferation arrest induced by ergosterol depletion.

Retinoblastoma gene product activates expression of the human TGF-β2 gene through transcription factor ATF-2

Nature ◽  
1992 ◽  
Vol 358 (6384) ◽  
pp. 331-334 ◽  
Author(s):  
Seong-Jin Kim ◽  
Susanne Wagner ◽  
Fang Liu ◽  
Michael A. O'Reilly ◽  
Paul D. Robbins ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Product ◽  
Retinoblastoma Gene ◽  
Retinoblastoma Gene Product

Deletions in the C-terminal coding region of the v-sis gene: dimerization is required for transformation

1986 ◽  
Vol 6 (4) ◽  
pp. 1304-1314
Author(s):  
M Hannink ◽  
M K Sauer ◽  
D J Donoghue
Keyword(s):  
Growth Factor ◽  
Gene Product ◽  
Platelet Derived Growth Factor ◽  
Deletion Mutants ◽  
Gene Products ◽  
Coding Region ◽  
Strong Connection ◽  
C Terminus ◽  
Its Gene ◽  
Transforming Gene

The v-sis gene encodes chain B of platelet-derived growth factor. However, this gene codes for additional amino acids at both the N terminus and the C terminus of its gene product which are not present in the amino acid sequence of platelet-derived growth factor. We constructed a series of deletion mutants with deletions in the v-sis gene in order to define the C-terminal limit of the v-sis gene product which is required for transformation. Deletion mutants of the v-sis gene which encoded truncated gene products up to 57 residues shorter than the v-siswt gene product were still able to transform cells. The minimal transforming region of the v-sis gene product contained six residues fewer than were present in chain B of platelet-derived growth factor. Only 10 residues, including the sequence Cys-Lys-Cys, separated the smallest transforming gene product from the largest nontransforming gene product. These cysteine residues were also important for dimerization of the v-sis gene product, since all of the nontransforming v-sis deletions were unable to form dimers when they were analyzed under nonreducing conditions. Our results suggest that there is a strong connection between transformation and dimerization.

Identification of distinct roles for separate E1A domains in disruption of E2F complexes

1993 ◽  
Vol 13 (11) ◽  
pp. 7029-7035
Author(s):  
M A Ikeda ◽  
J R Nevins
Keyword(s):  
Transcription Factor ◽  
Gene Product ◽  
Protein Complexes ◽  
Cyclin A ◽  
Regulatory Proteins ◽  
Retinoblastoma Gene ◽  
Adenovirus E1a ◽  
E2f Transcription Factor ◽  
Cdk2 Complex ◽  
Equilibrium Dissociation

The adenovirus E1A protein can disrupt protein complexes containing the E2F transcription factor in association with cellular regulatory proteins such as the retinoblastoma gene product (Rb) and the Rb-related p107 protein. Previous experiments have shown that the CR1 and CR2 domains of E1A are required for this activity. We now demonstrate that the CR2 domain is essential for allowing E1A to interact with the E2F-Rb or the E2F-p107-cyclin A-cdk2 complex. Multimeric complexes containing E1A can be detected when the CR1 domain has been rendered inactive by mutation. In addition, the E1A CR1 domain, but not the CR2 domain, is sufficient to prevent the interaction of E2F with Rb or p107. On the basis of these results, we suggest a model whereby the CR2 domain brings E1A to the E2F complexes and then, upon a normal equilibrium dissociation of Rb or p107 from E2F, the E1A CR1 domain is able to block the site of interaction on Rb or p107, thereby preventing the re-formation of the complexes.

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