Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we reported that glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) was a novel target for prolactin (PRL) in the mouse mammary gland. However, the signaling pathway by which PRL regulates GlyCAM 1 expression has not been specified. In the present study, we showed that PRL induced GlyCAM 1 expression in primary mammary epithelial cells of mice through the Janus kinase 2/signal transducer and activator of transcription 5 (Stat5) pathway. Deletion and site-directed mutagenesis analyses of the GlyCAM 1 promoter demonstrated that the two tandemly linked Stat5 binding sites [interferon-gamma-activated sequence 1 and -2 (GAS1 and GAS2)] in the proximal promoter region were crucial and synergistically responded to PRL. GAS2, a consensus GAS site, was essential and, by itself, weakly responded to PRL, whereas GAS1, a nonconsensus site, failed to respond to PRL but was indispensable for the maximal activity of the GlyCAM 1 promoter. Gel shift assays showed that probe containing GAS1 and GAS2 bound two Stat5 complexes, which represent Stat5 dimer and tetramer, respectively, while GAS2, by itself, bound Stat5 as a dimer only, and GAS1 showed no apparent binding activity. Interruption of tetramer formation by mutation of a tryptophan to alanine (W37A), and a leucine to serine (L83S) in the N terminus of Stat5A attenuated the synergistic effect between the two tandemly linked GAS sites. Overexpression of W37A and L83S mutants in primary mammary epithelial cells suppressed endogenous GlyCAM 1 expression.
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PMID:Two tandemly linked interferon-gamma-activated sequence elements in the promoter of glycosylation-dependent cell adhesion molecule 1 gene synergistically respond to prolactin in mouse mammary epithelial cells. 1286 89

Prolactin (PRL) modulates proliferation in the mammary gland and other tissues, in part through inducing transcription of cyclin D1, a key regulator of G(1) phase cell cycle progression. We showed previously that PRL, via Jak2, induces binding of Stat5 to a distal GAS site (GAS1) in the cyclin D1 promoter. However, full promoter activity requires additional regions, and in this paper we explored PRL-induced activity at sites other than GAS1. We defined a second PRL-responsive region spanning -254 to -180 that contains a second GAS site (GAS2) and an Oct-1 binding site. Although mutational analysis indicated independence from GAS2, proximal promoter activity remained Stat5-dependent, suggesting alternative mechanisms. EMSA showed that Oct-1 binds the -254 to -180 region and that PRL decreased Oct-1 binding, leading to increased PRL-responsiveness of the proximal cyclin D1 promoter in multiple cell lines. This suggests a role for Oct-1 in PRL-dependent control of cyclin D1 transcription.
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PMID:Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter. 1588 80

The GAS multigene family of Saccharomyces cerevisiae is composed of five paralogs (GAS1 to GAS5). GAS1 is the only one of these genes that has been characterized to date. It encodes a glycosylphosphatidylinositol-anchored protein functioning as a beta(1,3)-glucan elongase and required for proper cell wall assembly during vegetative growth. In this study, we characterize the roles of the GAS2 and GAS4 genes. These genes are expressed exclusively during sporulation. Their mRNA levels showed a peak at 7 h from induction of sporulation and then decreased. Gas2 and Gas4 proteins were detected and reached maximum levels between 8 and 10 h from induction of sporulation, a time roughly coincident with spore wall assembly. The double null gas2 gas4 diploid mutant showed a severe reduction in the efficiency of sporulation, an increased permeability of the spores to exogenous substances, and production of inviable spores, whereas the single gas2 and gas4 null diploids were similar to the parental strain. An analysis of spore ultrastructure indicated that the loss of Gas2 and Gas4 proteins affected the proper attachment of the glucan to the chitosan layer, probably as a consequence of the lack of coherence of the glucan layer. The ectopic expression of GAS2 and GAS4 genes in a gas1 null mutant revealed that these proteins are redundant versions of Gas1p specialized to function in a compartment at a pH value close to neutral.
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PMID:GAS2 and GAS4, a pair of developmentally regulated genes required for spore wall assembly in Saccharomyces cerevisiae. 1718 86

The multigene GAS family of Saccharomyces cerevisiae is constituted by five genes encoding GPI-anchored proteins required for cell wall or spore wall assembly. GAS1 and GAS5 are expressed in vegetative growth and repressed during sporulation, whereas GAS2 and GAS4 exhibit the opposite expression pattern. This study focuses on GAS3, a still poorly characterized member of the family. To date, attempts to reveal the glucan elongase activity typical of Gas proteins have been unsuccessful, suggesting that Gas3p is the only inactive member of the family. Here, we compared the mRNA levels of GAS1, GAS3 and GAS5 and demonstrate that GAS3 is the weakest-expressed paralogue in vegetative growth. Moreover, GAS3 mRNA increased during sporulation, showing a bimodal profile typical of the early-middle meiotic genes. GAS3 product was identified as a low-abundance, polydisperse mannoprotein. Loss of Gas3p did not affect growth and sporulation. The overexpression of GAS3, driven by the GAS1 promoter, slightly reduced growth rate in a wild-type strain and led to hyperaccumulation of Gas3p in the membranes and in the cell wall. To determine whether GAS3 could replace GAS1 function in vivo, GAS3 was also overexpressed in a gas1Delta mutant. Increased amounts of Gas3p were not only unable to complement the defects of the gas1Delta cells but exacerbated them. A mutated Gas3p-E283Q, where one of the catalytic glutamate residues essential for GH72 enzyme activity was replaced by glutamine, was also noxious to gas1Delta cells, indicating that the increased expression of Gas3p, rather than a potential activity, is deleterious for gas1Delta cells.
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PMID:GAS3, a developmentally regulated gene, encodes a highly mannosylated and inactive protein of the Gas family of Saccharomyces cerevisiae. 2064 Oct 27

Sporulation is a developmental variation of the yeast life cycle whereby four spores are produced within a diploid cell, with proliferation resuming after germination. The GAS family of glycosylphosphatidylinositol-anchored glucan-remodeling enzymes exemplifies functional interplay between paralogous genes during the yeast life cycle. GAS1 and GAS5 are expressed in vegetative cells and repressed during sporulation while GAS2 and GAS4 exhibit a reciprocal pattern. GAS3 is weakly expressed in all the conditions and encodes an inactive protein. Although Gas1p functions in cell wall formation, we show that it persists during sporulation but is relocalized from the plasma membrane to the epiplasm in a process requiring End3p-mediated endocytosis and the Sps1 protein kinase of the p21-activated kinase family. Some Gas1p is also newly synthesized and localized to the spore membrane, but this fraction is dispensable for spore formation. By way of contrast, the Gas2-Gas4 proteins, which are essential for spore wall assembly, are rapidly degraded after spore formation. On germination, Gas1p is actively synthesized and concentrated in the growing part of the spore, which is essential for its elongation. Thus Gas1p is the primary glucan-remodeling enzyme required in vegetative growth and during reentry into the proliferative state. The dynamic interplay among Gas proteins is crucial to couple glucan remodeling with morphogenesis in developmental transitions.
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PMID:Expression, stability, and replacement of glucan-remodeling enzymes during developmental transitions in Saccharomyces cerevisiae. 2138 12