{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:25:16Z","timestamp":1784913916803,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T00:00:00Z","timestamp":1614470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["EMR\/2015\/002483"],"award-info":[{"award-number":["EMR\/2015\/002483"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>DKK3 is a secreted protein, which belongs to a family of Wnt antagonists and acts as a potential tumor suppressor in gallbladder cancer. To further understand its tumor suppressor functions, we overexpressed DKK3 in 3 GBC cell lines. We have employed high-resolution mass spectrometry and tandem mass tag (TMT) multiplexing technology along with immobilized metal affinity chromatography to enrich phosphopeptides to check the downstream regulators. In this study, we reported for the first time the alteration in the phosphorylation of 14 kinases upon DKK3 overexpression. In addition, we observed DKK3 induced hyper phosphorylation of 2 phosphatases: PPP1R12A and PTPRA, which have not been reported previously. Canonical pathway analysis of altered molecules indicated differential enrichment of signaling cascades upon DKK3 overexpression in all the 3 cell lines. Protein kinase A signaling, Sirtuin signaling pathway, and Cell Cycle Control of Chromosomal Replication were observed to be differentially activated in the GBC cell lines. Our study revealed, DKK3 overexpression has differential effect based on the aggressive behavior of the cell lines. This study expands the understanding of DKK3-mediated signaling events and can be used as a primary factor for understanding the complex nature of this molecule.<\/jats:p>","DOI":"10.3390\/cells10030511","type":"journal-article","created":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T20:43:32Z","timestamp":1614545012000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8605-3100","authenticated-orcid":false,"given":"Kirti","family":"Gondkar","sequence":"first","affiliation":[{"name":"Institute of Bioinformatics, International Tech Park, Bangalore 560066, India"},{"name":"Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajanan","family":"Sathe","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, International Tech Park, Bangalore 560066, India"},{"name":"Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, India"},{"name":"Manipal Academy of Higher Education (MAHE), Manipal 576104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Joshi","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, International Tech Park, Bangalore 560066, India"},{"name":"Manipal Academy of Higher Education (MAHE), Manipal 576104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bipin","family":"Nair","sequence":"additional","affiliation":[{"name":"Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, India"},{"name":"Manipal Academy of Higher Education (MAHE), Manipal 576104, India"},{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8975-5108","authenticated-orcid":false,"given":"Prashant","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, International Tech Park, Bangalore 560066, India"},{"name":"Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam 690525, India"},{"name":"Manipal Academy of Higher Education (MAHE), Manipal 576104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7469","DOI":"10.1038\/sj.onc.1210054","article-title":"Function and biological roles of the Dickkopf family of Wnt modulators","volume":"25","author":"Niehrs","year":"2006","journal-title":"Oncogene"},{"key":"ref_2","first-page":"357","article-title":"Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction","volume":"391","author":"Glinka","year":"1998","journal-title":"Nat. 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