BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.

Breast tumor kinase (BRK), also known as protein tyrosine kinase 6 (PTK6), is a non-receptor tyrosine kinase overexpressed in more that 60% of human breast carcinomas. The overexpression of BRK has been shown to sensitize mammary epithelial cells to mitogenic signaling and to promote cell proliferat...

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Autores principales:	Sayem Miah, Raghuveera Kumar Goel, Chenlu Dai, Natasha Kalra, Erika Beaton-Brown, Edward T Bagu, Keith Bonham, Kiven E Lukong
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0eb0e42ee72c498a98472e66fd3b4c9a
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spelling	oai:doaj.org-article:0eb0e42ee72c498a98472e66fd3b4c9a2021-11-18T08:33:02ZBRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.1932-620310.1371/journal.pone.0087684https://doaj.org/article/0eb0e42ee72c498a98472e66fd3b4c9a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24523872/?tool=EBIhttps://doaj.org/toc/1932-6203Breast tumor kinase (BRK), also known as protein tyrosine kinase 6 (PTK6), is a non-receptor tyrosine kinase overexpressed in more that 60% of human breast carcinomas. The overexpression of BRK has been shown to sensitize mammary epithelial cells to mitogenic signaling and to promote cell proliferation and tumor formation. The molecular mechanisms of BRK have been unveiled by the identification and characterization of BRK target proteins. Downstream of tyrosine kinases 1 or Dok1 is a scaffolding protein and a substrate of several tyrosine kinases. Herein we show that BRK interacts with and phosphorylates Dok1 specifically on Y362. We demonstrate that this phosphorylation by BRK significantly downregulates Dok1 in a ubiquitin-proteasome-mediated mechanism. Together, these results suggest a novel mechanism of action of BRK in the promotion of tumor formation, which involves the targeting of tumor suppressor Dok1 for degradation through the ubiquitin proteasomal pathway.Sayem MiahRaghuveera Kumar GoelChenlu DaiNatasha KalraErika Beaton-BrownEdward T BaguKeith BonhamKiven E LukongPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e87684 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sayem Miah Raghuveera Kumar Goel Chenlu Dai Natasha Kalra Erika Beaton-Brown Edward T Bagu Keith Bonham Kiven E Lukong BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
description	Breast tumor kinase (BRK), also known as protein tyrosine kinase 6 (PTK6), is a non-receptor tyrosine kinase overexpressed in more that 60% of human breast carcinomas. The overexpression of BRK has been shown to sensitize mammary epithelial cells to mitogenic signaling and to promote cell proliferation and tumor formation. The molecular mechanisms of BRK have been unveiled by the identification and characterization of BRK target proteins. Downstream of tyrosine kinases 1 or Dok1 is a scaffolding protein and a substrate of several tyrosine kinases. Herein we show that BRK interacts with and phosphorylates Dok1 specifically on Y362. We demonstrate that this phosphorylation by BRK significantly downregulates Dok1 in a ubiquitin-proteasome-mediated mechanism. Together, these results suggest a novel mechanism of action of BRK in the promotion of tumor formation, which involves the targeting of tumor suppressor Dok1 for degradation through the ubiquitin proteasomal pathway.
format	article
author	Sayem Miah Raghuveera Kumar Goel Chenlu Dai Natasha Kalra Erika Beaton-Brown Edward T Bagu Keith Bonham Kiven E Lukong
author_facet	Sayem Miah Raghuveera Kumar Goel Chenlu Dai Natasha Kalra Erika Beaton-Brown Edward T Bagu Keith Bonham Kiven E Lukong
author_sort	Sayem Miah
title	BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
title_short	BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
title_full	BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
title_fullStr	BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
title_full_unstemmed	BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
title_sort	brk targets dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/0eb0e42ee72c498a98472e66fd3b4c9a
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BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration.

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