A gene family in<i>Drosophila melanogaster</i>coding for trypsin-like enzymes

Davis, Claytus; Riddell, D. Christie; Higgins, Michael J.; Holden, J. J. A.; White, Bradley N.

doi:10.1093/nar/13.18.6605

Cited by 98 publications

(74 citation statements)

References 45 publications

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“…The pancreatic endocrine function is served by cells in the brain that deliver insulinlike peptides to the heart tube and gut and neuroendocrine cells of the ring gland that release peptides with glucagon-like functions into the hemolymph (Rulifson et al 2002;Kim and Rulifson 2004). Although digestive serine proteases are produced in the ventriculus and gastric caecae (Davis et al 1985), Fer1 is not expressed there (http://flybase.bio.indiana.edu; J. Zoloty, R.J. MacDonald, and D.M. McKearin, unpubl.…”

Section: The Ptf1 Complex Has An Ancient Functionmentioning

confidence: 99%

Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex

et al. 2007

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PTF1a is an unusual basic helix-loop-helix (bHLH) transcription factor that is required for the development of the pancreas. We show that early in pancreatic development, active PTF1a requires interaction with RBPJ, the vertebrate Suppressor of Hairless, within a stable trimeric DNA-binding complex (PTF1). Later, as acinar cell development begins, RBPJ is swapped for RBPJL, the constitutively active, pancreas-restricted paralog of RBPJ. Moreover, the Rbpjl gene is a direct target of the PTF1 complex: At the onset of acinar cell development when the Rbpjl gene is first induced, a PTF1 complex containing RBPJ is bound to the Rbpjl promoter. As development proceeds, RBPJL gradually replaces RBPJ in the PTF1 complex bound to Rbpjl and appears on the binding sites for the complex in the promoters of other acinar-specific genes, including those for the secretory digestive enzymes. A single amino acid change in PTF1a that eliminates its ability to bind RBPJ (but does not affect its binding to RBPJL) causes pancreatic development to truncate at an immature stage, without the formation of acini or islets. These results indicate that the interaction between PTF1a and RBPJ is required for the early stage of pancreatic growth, morphogenesis, and lineage fate decisions. The defects in pancreatic development phenocopy those of Ptf1a-null embryos; thus, the first critical function of PTF1a is in the context of the PTF1 complex containing RBPJ. Action within an organ-specific transcription factor is a previously unknown function for RBPJ and is independent of its role in Notch signaling.[Keywords: Ptf1a; Rbpj; Notch signaling; basic helix-loop-helix; pancreas; acinar cell] Supplemental material is available at http://www.genesdev.org.

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Section: The Ptf1 Complex Has An Ancient Functionmentioning

confidence: 99%

Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex

et al. 2007

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“…(17); DMTRY, Drosophila trypsinlike enzyme (11); DMSNAK, Drosophila snake gene product (14); BOVCHY, bovine chymotrypsin; BOVTRY, bovine trypsin. cleavage, with the last residue of the activation peptide being a lysine or arginine.…”

Section: Ated (In Bases) Thementioning

confidence: 99%

Levels of RNA from a family of putative serine protease genes are reduced in Drosophila melanogaster dunce mutants and are regulated by cyclic AMP.

Yun¹,

Davis²

1989

Mol. Cell. Biol.

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We have isolated several genes expressed at abnormal levels in the memory mutant, dunce (dnc), of Drosophila melanogaster. These mutants have an elevated cyclic AMP (cAMP) content due to a mutation in the structural gene for cAMP phosphodiesterase, so the isolated genes are potentially ones regulated by cAMP. Here, we describe the characterization of a genomic clone and corresponding cDNA clones which contain sequences that are underexpressed in dnc mutants. Sequence analysis of portions of the genomic clone and representative cDNAs revealed the presence of two uninterrupted and complete open reading frames (SER1 and SER2) and part of a third (SER3). The predicted amino acid sequences of all of these were found to be homologous to the serine protease family of enzymes. The genomic clone was localized to the polytene chromosome region 99C-D, although genome-blotting experiments indicated the existence of several other genes related to the cloned serine protease-like genes. Hybridization experiments with probes representing each of the three sequenced genes showed that only the SERl-related genes were differentially expressed in dnc mutants. The putative serine protease genes were abundantly expressed in the larval gut, suggesting a major function in digestion. Feeding normal flies cAMP, isobutylmethylxanthine, or forskolin resulted in a decreased RNA level of the SERl-related genes. Thus, RNA levels of this serine protease gene family are negatively regulated by cAMP.Cyclic AMP (cAMP) has been shown to mediate many biological processes in diverse organisms. In procaryotes, cAMP and its receptor protein, CRP, modulate the transcriptional activity of a variety of genes (2). In eucaryotes, the molecule serves as an intracellular second messenger of external stimuli, including hormones and neurotransmitters. One important area of cAMP action currently under intensive study is its role in eucaryotic gene expression. cAMP has been shown, for example, to regulate the mRNA levels of the genes encoding the hormones preproenkephalin (10), gonadotropin (23), prolactin (34), somatostatin (36), vasoactive intestinal polypeptide (44), and growth hormone (47). The mRNA levels of these genes are regulated in a positive manner at least partly at the level of transcription. The RNA of the proto-oncogenes c-myc and c-fos can also be induced by increases in cAMP (5,19,38,43). Genes coding for key metabolic enzymes, including tyrosine aminotransferase, lactate dehydrogenase, tryosine hydroxylase, phosphoenol pyruvate carboxykinase, and dihydrofolate reductase (21,25,32,41,45,50), are regulated at the level of transcription by cAMP in either a positive or a negative way. In addition, the mRNA levels of tubulin and actin, the main protein constituents of microtubules and microfilaments, are modulated by cAMP (16). Thus, cAMP modulates the activity of various genes by altering mRNA abundance, either positively or negatively, and in most cases this modulation occurs at least in part at the level of transcription. The * Corresponding auth...

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“…The serine protease genes that have been cloned and sequenced show extensive regions of sequence similarity, including a characteristic Asp-Ser-(His/Gly) tripeptide at the active site (6,9). Nucleotide sequence data have only been reported for one eukaryotic esterase, acetyicholinesterase from the ray Torpedo californica (8).…”

Section: (4)mentioning

confidence: 99%

Molecular cloning and characterization of esterase-6, a serine hydrolase of Drosophila.

Oakeshott¹,

Collet²,

Phillis³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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The Est-6 gene of Drosophila melanogaster was cloned by screening libraries with synthetic oligonucleotides corresponding to tryptic peptides from purified esterase-6 (Est-6) protein. cDNA clones were isolated that hybridized in situ to the site of Est-6 on chromosome 3 at 69A1. Inserts in putative Est-6 cDNA clones were 1.85 kilobases (kb) long, and blot hybridization analysis of electrophoretically fractionated RNA, using a cDNA done as a probe, revealed two transcripts, of 1.68 and 1.83 kb. The two transcripts showed the same developmental profile as the Est-6 protein. Neither transcript was detected in an Est-6-null line. The cDNA fragment was homologous to a 2.3-kb EcoRI-BamHI fragment in genomic clones, and this region was interrupted by the 8-kb B104 transposable element in the Est-6-null line. Conceptual translation of the cDNA sequence revealed a protein of 548 residues with 19% sequence similarity to acetylcholinesterase from the Torpedo ray.Esterase-6 (Est-6; carboxylic-ester hydrolase, E.C. 3.1.1.1), the major, -carboxylesterase ofDrosophila melanogaster, is produced as a monomer in the anterior ejaculatory duct ofthe male reproductive system and plays an important role in its reproductive biology (1,2). There is considerable polymorphism at the Est-6 locus in natural populations for activity and electrophoretic mobility of the enzyme, and at least some of this variation is subject to natural selection (3). Moreover, there are qualitative differences between D. melanogaster and its sibling species in the structure and expression of (4). This paper describes the cloning and initial characterization ofthe Est-6 gene ofD. melanogaster. This opens the way for a study of the molecular basis of the evolution of Est-6 structural and regulatory sequences in Drosophila, although this report focuses on the more distant origins and relationships of the locus. In particular, the Est-6 cDNA sequence has been analyzed for sequence similarity with members of the serine hydrolase family of enzymes.The serine hydrolases are presently defined as a functionally related class of hydrolytic enzymes containing a serine residue in their active site (5). The class comprises the relatively well-characterized serine protease multigene family (6) as well as various carboxyl-, choline-, and aliesterases (7,8). Despite their functional and structural similarities, it is not clear whether any of the various esterases are genetically related to each other or to the serine proteases, or whether their similarities are the outcome of convergent evolution.The serine protease genes that have been cloned and sequenced show extensive regions of sequence similarity, including a characteristic Asp-Ser-(His/Gly) tripeptide at the active site (6, 9). Nucleotide sequence data have only been reported for one eukaryotic esterase, acetyicholinesterase from the ray Torpedo californica (8). This enzyme shows very little sequence similarity to the serine proteases and contains a Glu-Ser-Ala tripeptide at the active site.The sequences of up...

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A gene family inDrosophila melanogastercoding for trypsin-like enzymes

Cited by 98 publications

References 45 publications

Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex

Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex

Levels of RNA from a family of putative serine protease genes are reduced in Drosophila melanogaster dunce mutants and are regulated by cyclic AMP.

Molecular cloning and characterization of esterase-6, a serine hydrolase of Drosophila.

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