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  Formin-like 2 promotes beta 1-integrin trafficking and invasive motility downstream of PKC alpha.

Wang, Y., Arjonen, A., Pouwels, J., Ta, H., Pausch, P., Bange, G., et al. (2015). Formin-like 2 promotes beta 1-integrin trafficking and invasive motility downstream of PKC alpha. Developmental Cell, 34(4), 475-483. doi:10.1016/j.devcel.2015.06.015.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-5BB9-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-6000-2
Genre: Journal Article

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 Creators:
Wang, Y., Author
Arjonen, A., Author
Pouwels, J., Author
Ta, H.1, Author              
Pausch, P., Author
Bange, G., Author
Engel, U., Author
Pan, X. Y., Author
Fackler, O. T., Author
Ivaska, J., Author
Grosse, R., Author
Affiliations:
1Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society, ou_578627              

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 Abstract: Regulated turnover of integrin receptors is essential for cell adhesion and migration. Pathways selectively regulating beta 1-integrin recycling are implicated in cancer invasion and metastasis, yet proteins required for the internalization of this pro-invasive integrin remain to be identified. Here, we uncover formin-like 2 (FMNL2) as a critical regulator of beta 1-integrin internalization downstream of protein kinase C (PKC). PKC alpha associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition. Phosphorylation of FMNL2 triggers its rapid relocation and promotes its interaction with the cytoplasmic tails of the a-integrin subunits for beta 1-integrin endocytosis. FMNL2 drives beta 1-integrin internalization and invasive motility in a phosphorylationdependent manner, while a FMNL2 mutant defective in actin assembly interferes with beta 1-integrin endocytosis and cancer cell invasion. Our data establish a role for FMNL2 in the regulation of beta 1-integrin and provide a mechanistic understanding of the function of FMNL2 in cancer invasiveness.

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Language(s): eng - English
 Dates: 2015-08-24
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.devcel.2015.06.015
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Title: Developmental Cell
Source Genre: Journal
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Pages: - Volume / Issue: 34 (4) Sequence Number: - Start / End Page: 475 - 483 Identifier: -