Altered signaling associated with chronic arsenic exposure in human skin keratinocytes

Sartaj Ahmad Mir; Santosh Renuse; Gajanan Sathe; Aafaque Ahmad Khan; Arun H. Patil; Vishalakshi Nanjappa; Firdous Ahmad Bhat; T. S.Keshava Prasad; Ashok K. Giri; Aditi Chatterjee; Harsha Gowda

doi:10.1002/prca.201700004

Altered signaling associated with chronic arsenic exposure in human skin keratinocytes

Sartaj Ahmad Mir, Santosh Renuse, Gajanan Sathe, Aafaque Ahmad Khan, Arun H. Patil, Vishalakshi Nanjappa, Firdous Ahmad Bhat, T. S.Keshava Prasad, Ashok K. Giri, Aditi Chatterjee, Harsha Gowda

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

Abstract

Modulation of signaling pathways upon chronic arsenic exposure remains poorly studied. Here, we carried out SILAC-based quantitative phosphoproteomics analysis to dissect the signaling induced upon chronic arsenic exposure in human skin keratinocyte cell line, HaCaT. We identified 4171 unique phosphosites derived from 2000 proteins. We observed differential phosphorylation of 406 phosphosites (twofold) corresponding to 305 proteins. Several pathways involved in cytoskeleton maintenance and organization were found to be significantly enriched (p<0.05). Our data revealed altered phosphorylation of proteins associated with adherens junction remodeling and actin polymerization. Kinases such as protein kinase C iota type (PRKCI), mitogen-activated protein kinase kinase kinase 1 (MAP3K1), tyrosine-protein kinase BAZ1B (BAZ1B) and STE20 like kinase (SLK) were found to be hyperphosphorylated. Our study provides novel insights into signaling perturbations associated with chronic arsenic exposure in human skin keratinocytes. All MS/MS data have been deposited to the ProteomeXchange with identifier PXD004868.

Original language	English (US)
Article number	1700004
Journal	Proteomics - Clinical Applications
Volume	11
Issue number	11-12
DOIs	https://doi.org/10.1002/prca.201700004
State	Published - Dec 2017

Keywords

Arsenite
Mass spectrometry
Metabolic labeling
Phosphoproteome
Titanium-dioxide

ASJC Scopus subject areas

Clinical Biochemistry

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10.1002/prca.201700004

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title = "Altered signaling associated with chronic arsenic exposure in human skin keratinocytes",

abstract = "Modulation of signaling pathways upon chronic arsenic exposure remains poorly studied. Here, we carried out SILAC-based quantitative phosphoproteomics analysis to dissect the signaling induced upon chronic arsenic exposure in human skin keratinocyte cell line, HaCaT. We identified 4171 unique phosphosites derived from 2000 proteins. We observed differential phosphorylation of 406 phosphosites (twofold) corresponding to 305 proteins. Several pathways involved in cytoskeleton maintenance and organization were found to be significantly enriched (p<0.05). Our data revealed altered phosphorylation of proteins associated with adherens junction remodeling and actin polymerization. Kinases such as protein kinase C iota type (PRKCI), mitogen-activated protein kinase kinase kinase 1 (MAP3K1), tyrosine-protein kinase BAZ1B (BAZ1B) and STE20 like kinase (SLK) were found to be hyperphosphorylated. Our study provides novel insights into signaling perturbations associated with chronic arsenic exposure in human skin keratinocytes. All MS/MS data have been deposited to the ProteomeXchange with identifier PXD004868.",

keywords = "Arsenite, Mass spectrometry, Metabolic labeling, Phosphoproteome, Titanium-dioxide",

author = "Mir, {Sartaj Ahmad} and Santosh Renuse and Gajanan Sathe and Khan, {Aafaque Ahmad} and Patil, {Arun H.} and Vishalakshi Nanjappa and Bhat, {Firdous Ahmad} and Prasad, {T. S.Keshava} and Giri, {Ashok K.} and Aditi Chatterjee and Harsha Gowda",

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year = "2017",

month = dec,

doi = "10.1002/prca.201700004",

language = "English (US)",

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journal = "Proteomics - Clinical Applications",

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AU - Mir, Sartaj Ahmad

AU - Renuse, Santosh

AU - Sathe, Gajanan

AU - Khan, Aafaque Ahmad

AU - Patil, Arun H.

AU - Nanjappa, Vishalakshi

AU - Bhat, Firdous Ahmad

AU - Prasad, T. S.Keshava

AU - Giri, Ashok K.

AU - Chatterjee, Aditi

AU - Gowda, Harsha

PY - 2017/12

Y1 - 2017/12

N2 - Modulation of signaling pathways upon chronic arsenic exposure remains poorly studied. Here, we carried out SILAC-based quantitative phosphoproteomics analysis to dissect the signaling induced upon chronic arsenic exposure in human skin keratinocyte cell line, HaCaT. We identified 4171 unique phosphosites derived from 2000 proteins. We observed differential phosphorylation of 406 phosphosites (twofold) corresponding to 305 proteins. Several pathways involved in cytoskeleton maintenance and organization were found to be significantly enriched (p<0.05). Our data revealed altered phosphorylation of proteins associated with adherens junction remodeling and actin polymerization. Kinases such as protein kinase C iota type (PRKCI), mitogen-activated protein kinase kinase kinase 1 (MAP3K1), tyrosine-protein kinase BAZ1B (BAZ1B) and STE20 like kinase (SLK) were found to be hyperphosphorylated. Our study provides novel insights into signaling perturbations associated with chronic arsenic exposure in human skin keratinocytes. All MS/MS data have been deposited to the ProteomeXchange with identifier PXD004868.

AB - Modulation of signaling pathways upon chronic arsenic exposure remains poorly studied. Here, we carried out SILAC-based quantitative phosphoproteomics analysis to dissect the signaling induced upon chronic arsenic exposure in human skin keratinocyte cell line, HaCaT. We identified 4171 unique phosphosites derived from 2000 proteins. We observed differential phosphorylation of 406 phosphosites (twofold) corresponding to 305 proteins. Several pathways involved in cytoskeleton maintenance and organization were found to be significantly enriched (p<0.05). Our data revealed altered phosphorylation of proteins associated with adherens junction remodeling and actin polymerization. Kinases such as protein kinase C iota type (PRKCI), mitogen-activated protein kinase kinase kinase 1 (MAP3K1), tyrosine-protein kinase BAZ1B (BAZ1B) and STE20 like kinase (SLK) were found to be hyperphosphorylated. Our study provides novel insights into signaling perturbations associated with chronic arsenic exposure in human skin keratinocytes. All MS/MS data have been deposited to the ProteomeXchange with identifier PXD004868.

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KW - Metabolic labeling

KW - Phosphoproteome

KW - Titanium-dioxide

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Altered signaling associated with chronic arsenic exposure in human skin keratinocytes

Abstract

Keywords

ASJC Scopus subject areas

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