Elbediwy, A. and Zhang, Y. and Cobbaut, M. and Riou, P. and Tan, R.S. and Roberts, S.K. and Tynan, C. and George, R. and Kjaer, S. and Martin-Fernandez, M.L. and Thompson, B.J. and McDonald, Neil Q. and Parker, P.J. (2019) The Rho-family GEF FARP2 is activated by aPKCiota to control polarity and tight junction formation. Journal of Cell Science 132 (8), jcs223743. ISSN 0021-9533.
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Abstract
The elaboration of polarity is central to organismal development and to the maintenance of functional epithelia. Amongst the controls determining polarity are the PAR proteins, PAR6/aPKCiota-PAR3, regulating both known and unknown effectors. Here we identify FARP2 as a "RIPR" motif dependent partner and substrate of aPKCiota that is required for efficient polarisation and junction formation. Binding is conferred by a FERM/FA domain-Kinase domain interaction and detachment promoted by aPKCiota dependent phosphorylation. FARP2 is shown to promote GTP loading of Cdc42 consistent with upstream regulation of the polarising PAR6-aPKCiota complex. However, it is shown that aPKCiota acts to promote the localised activity of FARP2 through phosphorylation. We conclude that this aPKCiota FARP2 complex formation acts as a positive feedback control to drive polarisation through aPKCiota and other Cdc42 effectors. Ahmed , Yixiao , Mathias , Philippe , Ray S. , Selene K. Roberts, Chris Tynan, Roger George, Svend Kjaer, Marisa L. Martin-Fernandez, Barry J. Thompson, Neil Q. McDonald, Peter J. Parker
Metadata
Item Type: | Article |
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Keyword(s) / Subject(s): | Cdc42, FARP, Atypical protein kinase C, Polarity |
School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
Depositing User: | Neil Mcdonald |
Date Deposited: | 29 Mar 2019 14:48 |
Last Modified: | 02 Aug 2023 17:50 |
URI: | https://eprints.bbk.ac.uk/id/eprint/26969 |
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