PKA phosphorylation of p62/SQSTM1 regulates PB1 domain interaction partner binding

Authors / Editors

Krause, Elvis Tim

Research Areas

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Publication Details

Output type: Journal article

Author list: Christian F, Krause E, Houslay MD, Baillie GS

Publisher: Elsevier

Publication year: 2014

Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (0167-4889)

Volume number: 1843

Issue number: 11

Start page: 2765

End page: 2774

Number of pages: 10

ISSN: 0167-4889

Languages: English-Great Britain (EN-GB)

Unpaywall Data

Open access status: hybrid

Full text URL: https://doi.org/10.1016/j.bbamcr.2014.07.021

Abstract

p62, also known as SQSTM1, is a multi-domain signalling scaffold protein involved in numerous critical cellular functions such as autophagy, apoptosis and inflammation. Crucial interactions relevant to these functions are mediated by the N-terminal Phox and Bem1p (PB1) domain, which is divided into two interaction surfaces, one of predominantly acidic and one of basic character. Most known interaction partners, including atypical protein kinase C (aPKC), bind to the basic surface, and acidic-basic interactions at this interface also allow for p62 homopolymerisation. We identify here that the coupling of p62 to the cAMP signalling system is conferred by both the direct binding of cAMP degrading phosphodiesterase-4 (PDE4) to the acidic surface of the p62 PB1 domain and the phosphorylation of the basic surface of this domain by CAMP-dependent protein kinase (PKA). Such phosphoiylation is a previously unknown means of regulating PB1 domain interaction partnerships by disrupting the interaction of p62 with basic surface binding partners, such as aPKCs, as well as p62 homopolymerisation. Thus, we uncover a new regulatory mechanism that connects cAMP signalling with the p62 multi-domain signalling scaffold and autophagy cargo receptor protein. (C) 2014 Elsevier B.V. All rights reserved.

Keywords

Autophagy, cAMP signalling, p62, Phosphodiesterase, Protein kinase A, Protein-protein interaction

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