The Drosophila Gene hid Is a Direct Molecular Target of Ras-Dependent Survival Signaling

Bergmann, Andreas; Agapite, Julie; McCall, Kimberly; Steller, Hermann

doi:10.1016/s0092-8674(00)81765-1

Cited by 454 publications

(432 citation statements)

References 57 publications

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“…The Ras-MAPK pathway has been shown to promote cell survival in many di erent systems (Xia et al, 1995;Gardner and Johnson, 1996;Parrizas et al, 1997;Kurada and White, 1998;Bergmann et al, 1998). There has been a lack of functional connection between the Ras-MAPK pathway and a pro-apoptotic molecule or death antagonist of the BCL-2 family although the Ras-MAPK pathway has been shown to down-regulate the proapoptotic activity of the gene head involution defective (hid) (Kurada and White, 1998;Bergmann et al, 1998). Our results suggest that BAD may not only provide a relay for the antiapoptotic activity of Akt, but also act as a potential e ector for MAPKmediated suppression of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…The Ras-MAPK signaling pathway is essential for cell proliferation and differentiation (Cowley et al, 1994). It also plays an important role in the regulation of cell survival (Xia et al, 1995;Gardner and Johnson, 1996;Parrizas et al, 1997;Bergmann et al, 1998). MAPK activity was examined in HEK293 cells stimulated with EGF, IGF-I or insulin using a phospho-speci®c antibody and by means of gel-mobility shift assays.…”

Section: Bad Phosphorylation At Ser-112 Correlates With Activation Ofmentioning

confidence: 99%

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Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway

et al. 1999

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The function of the pro-apoptotic molecule BAD is regulated by phosphorylation of two sites, serine-112 (Ser-112) and . Phosphorylation at either site results in loss of the ability of BAD to heterodimerize with the survival proteins BCL-X L or BCL-2. Phosphorylated BAD binds to 14-3-3 and is sequestered in the cytoplasm. It has been shown that phosphorylation of BAD at Ser-136 is mediated by the serine/threonine protein kinase Akt-1/PKB which is downstream of phosphatidylinositol 3-kinase (PI3K). The signaling process leading to phosphorylation of BAD at Ser-112 has not been identi®ed. In this study, we show that phosphorylation of the two serine residues of BAD is di erentially regulated. While Ser-136 phosphorylation is concordant with activation of Akt, Ser-112 phosphorylation does not correlate with Akt activation. Instead, we demonstrate that activated Ras and Raf, which are upstream of mitogen-activated protein kinases (MAPK), stimulate selective phosphorylation of BAD at Ser-112. Furthermore, phosphorylation of Ser-112, but not Ser-136 requires activation of the MAPK pathway as the MEK inhibitor, PD 98059, blocks EGF-, as well as activated Ras-or Raf-mediated phosphorylation of BAD at Ser-112. Therefore, the PI3K-Akt and Ras-MAPK pathways converge at BAD by mediating phosphorylation of distinct serine residues.

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Section: Discussionmentioning

confidence: 99%

Section: Bad Phosphorylation At Ser-112 Correlates With Activation Ofmentioning

confidence: 99%

Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway

et al. 1999

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“…According to this hypothesis, the primary function of EGFR during ommatidial assembly might be to prevent apoptosis, thereby allowing cells to adopt appropriate cell fates in response to other signaling cues. Supporting this idea, it is well established that EGFR signaling inhibits apoptosis in the eye (Bergmann et al, 1998;Kurada and White, 1998;Baker and Yu, 2001). For example, no cells from Egfr null clones survive to adulthood, pre-sumably because these clones undergo extensive programmed cell death soon after the MF has passed (Xu and Rubin, 1993;Dominguez et al, 1998).…”

Section: Egfr Signaling Is Required For All Eye Cell Fates Except R8:mentioning

confidence: 91%

Signal integration during development: Insights from the Drosophila eye

Voas

Rebay

2003

Developmental Dynamics

162

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The Drosophila eye is a highly ordered epithelial tissue composed of ϳ750 subunits called ommatidia arranged in a reiterated hexagonal pattern. At higher resolution, observation of the constituent photoreceptors, cone cells, and pigment cells of the eye reveals a highly ordered mosaic of amazing regularity. This relatively simple organization belies the repeated requirement for spatially and temporally coordinated inputs from the Hedgehog (Hh), Wingless (Wg), Decapentaplegic (Dpp), JAK-STAT, Notch, and receptor tyrosine kinase (RTK) signaling pathways. This review will discuss how signaling inputs from the Notch and RTK pathways, superimposed on the developmental history of a cell, facilitate context-specific and appropriate cell fate specification decisions in the developing fly eye. Lessons learned from investigating the combinatorial signal integration strategies underlying Drosophila eye development will likely reveal cell-cell communication paradigms relevant to many aspects of invertebrate and mammalian development. Developmental Dynamics 229:162-175, 2004.

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“…Several laboratories have demonstrated that signaling from the Drosophila epidermal growth factor receptor (dEgfr/ DER/Torpedo/Flb)/ras pathway promotes lattice cell life, [13][14][15][16] in part through negative regulation of the cell death effector head involution defective (HID). 17,18 During the period of lattice cell death, dEgfr is expressed by all lattice cells, and its soluble ligand, Spitz (Spi), is expressed by cone cells and primary pigment cells. 13 Counteracting the dEgfr/ras pathway is the Notch signaling pathway that directs lattice cell death.…”

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confidence: 99%

Identification of the death zone: a spatially restricted region for programmed cell death that sculpts the fly eye

Monserrate

Brachmann

2006

Cell Death Differ

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Programmed cell death (PCD) sculpts many developing tissues. The final patterning step of the Drosophila retina is the elimination, through PCD, of a subset of interommatidial lattice cells during pupation. It is not understood how this process is spatially regulated to ensure that cells die in the proper positions. To address this, we observed PCD of lattice cells in the pupal retina in real time. This live-visualization method demonstrates that lattice cell apoptosis is a highly specific process. In all, 85% of lattice cells die in exclusive 'death zone' positions between adjacent ommatidia. In contrast, cells that make specific contacts with primary pigment cells are protected from death. Two signaling pathways, Drosophila epidermal growth factor receptor (dEgfr) and Notch, that are thought to be central to the regulation of lattice cell survival and death, are not sufficient to establish the death zone. Thus, application of live visualization to the fly eye gives new insight into a dynamic developmental process.

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The Drosophila Gene hid Is a Direct Molecular Target of Ras-Dependent Survival Signaling

Cited by 454 publications

References 57 publications

Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway

Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway

Signal integration during development: Insights from the Drosophila eye

Identification of the death zone: a spatially restricted region for programmed cell death that sculpts the fly eye

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