Src kinases and ERK activate distinct responses to Stitcher receptor tyrosine kinase signaling during wound healing in <i>Drosophila</i>

Tsarouhas, Vasilios; Yao, Liqun; Samakovlis, Christos

doi:10.1242/jcs.143016

Cited by 28 publications

(26 citation statements)

References 54 publications

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“…5). One pathway operates via the Stitcher Receptor Tyrosine Kinase through the downstream effectors DRK, Src42A, and ERK to the Grainy head transcription factor (12,34,35). DNA binding sites for Grainy head are commonly found in, and are required for the function of some wound-activated epidermal repair genes, in Drosophila and mammals (11,12,14).…”

Section: Discussionmentioning

confidence: 99%

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

Capilla

Karachentsev

Patterson

et al. 2017

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

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The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor. Epistasis experiments indicate a requirement for Spätzle ligand downstream of hydrogen peroxide and protease function, both of which are known activators of wound-induced transcription. The localized activation of Toll a few cell diameters from wound edges is reminiscent of local activation of Toll in early embryonic ventral hypoderm, consistent with the hypothesis that the dorsal–ventral patterning function of Toll arose from the evolutionary cooption of a morphogen-responsive function in wound repair. Furthermore, the combinatorial activity of Toll and other signaling pathways in activating epidermal barrier repair genes can help explain why developmental activation of the Toll, ERK, or JNK pathways alone fail to activate wound repair loci.

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Section: Discussionmentioning

confidence: 99%

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

Capilla

Karachentsev

Patterson

et al. 2017

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

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“…molecular repulsion need not be invoked. Biologically values of the H coef below 1 or negative correlations can originate from opposing concentration gradients of morphogens but these are not attributable to repulsion [22]. An enzyme transforming a substrate could also produce a negative correlation or an H coef below 1, independently of repulsion.…”

Section: Discussionmentioning

confidence: 99%

Quantifying Colocalization: Thresholding, Void Voxels and the Hcoef

Adler

Parmryd

2014

PLoS ONE

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A critical step in the analysis of images is identifying the area of interest e.g. nuclei. When the nuclei are brighter than the remainder of the image an intensity can be chosen to identify the nuclei. Intensity thresholding is complicated by variations in the intensity of individual nuclei and their intensity relative to their surroundings. To compensate thresholds can be based on local rather than global intensities. By testing local thresholding methods we found that the local mean performed poorly while the Phansalkar method and a new method based on identifying the local background were superior. A new colocalization coefficient, the Hcoef, highlights a number of controversial issues. (i) Are molecular interactions measurable (ii) whether to include voxels without fluorophores in calculations, and (iii) the meaning of negative correlations. Negative correlations can arise biologically (a) because the two fluorophores are in different places or (b) when high intensities of one fluorophore coincide with low intensities of a second. The cases are distinct and we argue that it is only relevant to measure correlation using pixels that contain both fluorophores and, when the fluorophores are in different places, to just report the lack of co-occurrence and omit these uninformative negative correlation. The Hcoef could report molecular interactions in a homogenous medium. But biology is not homogenous and distributions also reflect physico-chemical properties, targeted delivery and retention. The Hcoef actually measures a mix of correlation and co-occurrence, which makes its interpretation problematic and in the absence of a convincing demonstration we advise caution, favouring separate measurements of correlation and of co-occurrence.

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“…The dominant negative mutant of AMPK-α1 (AMPK-α1-T172A-flag, “dn-AMPK-α1-flag”), created by mutating the Thr172 residue into Ala [48, 49], was provided by Dr. Wang [50]. The plasmid encoding a constitutively-active mutant of AMPKα1 (T172D, Ad-ca-AMPKα1-puromycin) and the empty vector (Ad) were also provided by Dr. Wang [50].…”

Section: Methodsmentioning

confidence: 99%

Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells

Xie

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). Methods: MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. Results: MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. Conclusion: MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling.

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Src kinases and ERK activate distinct responses to Stitcher receptor tyrosine kinase signaling during wound healing in Drosophila

Cited by 28 publications

References 54 publications

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

Quantifying Colocalization: Thresholding, Void Voxels and the Hcoef

Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells

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