A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.

Previous studies have shown that the cell polarity regulator hScrib interacts with, and consequently controls, the ERK signaling pathway. This interaction occurs through two well-conserved Kinase Interacting Motifs, which allow hScrib to bind ERK1 directly, resulting in a reduction in the levels of...

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Autores principales:	Kazunori Nagasaka, Takayuki Seiki, Aki Yamashita, Paola Massimi, Vanitha Krishna Subbaiah, Miranda Thomas, Christian Kranjec, Kei Kawana, Shunsuke Nakagawa, Tetsu Yano, Yuji Taketani, Tomoyuki Fujii, Shiro Kozuma, Lawrence Banks
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/45f0a6cc2a42441295e27e347cd5a114
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spelling	oai:doaj.org-article:45f0a6cc2a42441295e27e347cd5a1142021-11-18T08:00:12ZA novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.1932-620310.1371/journal.pone.0053752https://doaj.org/article/45f0a6cc2a42441295e27e347cd5a1142013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23359326/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Previous studies have shown that the cell polarity regulator hScrib interacts with, and consequently controls, the ERK signaling pathway. This interaction occurs through two well-conserved Kinase Interacting Motifs, which allow hScrib to bind ERK1 directly, resulting in a reduction in the levels of phospho-ERK. This suggests that hScrib might recruit a phosphatase to regulate this signaling pathway. Using a proteomic approach we now show that Protein Phosphatase 1γ (PP1γ) is a major interacting partner of hScrib. This interaction is direct and occurs through a conserved PP1γ interaction motif on the hScrib protein, and this interaction appears to be required for hScrib's ability to downregulate ERK phosphorylation. In addition, hScrib also controls the pattern of PP1γ localization, where loss of hScrib enhances the nuclear translocation of PP1γ. Furthermore, we also show that the ability of hScrib to interact with PP1γ is important for the ability of hScrib to suppress oncogene-induced transformation of primary rodent cells. Taken together, these results demonstrate that hScrib acts as a scaffold to integrate the control of the PP1γ and ERK signaling pathways and explains how disruption of hScrib localisation can contribute towards the development of human malignancy.Kazunori NagasakaTakayuki SeikiAki YamashitaPaola MassimiVanitha Krishna SubbaiahMiranda ThomasChristian KranjecKei KawanaShunsuke NakagawaTetsu YanoYuji TaketaniTomoyuki FujiiShiro KozumaLawrence BanksPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53752 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazunori Nagasaka Takayuki Seiki Aki Yamashita Paola Massimi Vanitha Krishna Subbaiah Miranda Thomas Christian Kranjec Kei Kawana Shunsuke Nakagawa Tetsu Yano Yuji Taketani Tomoyuki Fujii Shiro Kozuma Lawrence Banks A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.
description	Previous studies have shown that the cell polarity regulator hScrib interacts with, and consequently controls, the ERK signaling pathway. This interaction occurs through two well-conserved Kinase Interacting Motifs, which allow hScrib to bind ERK1 directly, resulting in a reduction in the levels of phospho-ERK. This suggests that hScrib might recruit a phosphatase to regulate this signaling pathway. Using a proteomic approach we now show that Protein Phosphatase 1γ (PP1γ) is a major interacting partner of hScrib. This interaction is direct and occurs through a conserved PP1γ interaction motif on the hScrib protein, and this interaction appears to be required for hScrib's ability to downregulate ERK phosphorylation. In addition, hScrib also controls the pattern of PP1γ localization, where loss of hScrib enhances the nuclear translocation of PP1γ. Furthermore, we also show that the ability of hScrib to interact with PP1γ is important for the ability of hScrib to suppress oncogene-induced transformation of primary rodent cells. Taken together, these results demonstrate that hScrib acts as a scaffold to integrate the control of the PP1γ and ERK signaling pathways and explains how disruption of hScrib localisation can contribute towards the development of human malignancy.
format	article
author	Kazunori Nagasaka Takayuki Seiki Aki Yamashita Paola Massimi Vanitha Krishna Subbaiah Miranda Thomas Christian Kranjec Kei Kawana Shunsuke Nakagawa Tetsu Yano Yuji Taketani Tomoyuki Fujii Shiro Kozuma Lawrence Banks
author_facet	Kazunori Nagasaka Takayuki Seiki Aki Yamashita Paola Massimi Vanitha Krishna Subbaiah Miranda Thomas Christian Kranjec Kei Kawana Shunsuke Nakagawa Tetsu Yano Yuji Taketani Tomoyuki Fujii Shiro Kozuma Lawrence Banks
author_sort	Kazunori Nagasaka
title	A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.
title_short	A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.
title_full	A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.
title_fullStr	A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.
title_full_unstemmed	A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.
title_sort	novel interaction between hscrib and pp1γ downregulates erk signaling and suppresses oncogene-induced cell transformation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/45f0a6cc2a42441295e27e347cd5a114
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A novel interaction between hScrib and PP1γ downregulates ERK signaling and suppresses oncogene-induced cell transformation.

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