Phosphorylation of serine 4642 in the C-terminus of plectin by MNK2 and PKA modulates its interaction with intermediate filaments

Bouameur, Jamal-Eddine; Schneider, Yann; Begré, Nadja; Hobbs, Ryan P.; Lingasamy, Prakash; Fontao, Lionel; Green, Kathleen J.; Favre, Bertrand; Borradori, Luca (2013). Phosphorylation of serine 4642 in the C-terminus of plectin by MNK2 and PKA modulates its interaction with intermediate filaments. Journal of cell science, 126(18), pp. 4195-4207. Company of Biologists Limited 10.1242/jcs.127779

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Plectin is a versatile cytolinker of the plakin family conferring cell resilience to mechanical stress in stratified epithelia and muscles. It acts as a critical organizer of the cytoskeletal system by tethering various intermediate filament (IF) networks through its C-terminal IF-binding domain (IFBD). Mutations affecting the IFBD cause devastating human diseases. Here, we show that serine 4642, which is located in the extreme C-terminus of plectin, is phosphorylated in different cell lines. Phosphorylation of S4642 decreased the ability of plectin IFBD to associate with various IFs, as assessed by immunofluorescence microscopy and cell fractionation studies, as well as in yeast two-hybrid assays. Plectin phosphorylated at S4642 was reduced at sites of IF network anchorage along cell-substrate contacts in both skin and cultured keratinocytes. Treatment of SK-MEL-2 and HeLa cells with okadaic acid increased plectin S4642 phosphorylation, suggesting that protein phosphatase 2A dephosphorylates this residue. Moreover, plectin S4642 phosphorylation was enhanced after cell treatment with EGF, phorbol ester, sorbitol and 8-bromo-cyclic AMP, as well as during wound healing and protease-mediated cell detachment. Using selective protein kinase inhibitors, we identified two different kinases that modulate the phosphorylation of plectin S4642 in HeLa cells: MNK2, which is downstream of the ERK1/2-dependent MAPK cascade, and PKA. Our study indicates that phosphorylation of S4642 has an important regulatory role in the interaction of plectin with IFs and identifies a novel link between MNK2 and the cytoskeleton.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Bouameur, Jamal-Eddine; Lingasamy, Prakash; Favre, Bertrand and Borradori, Luca

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0021-9533

Publisher:

Company of Biologists Limited

Language:

English

Submitter:

Monika Schenk

Date Deposited:

16 Jun 2014 10:27

Last Modified:

19 Oct 2015 11:32

Publisher DOI:

10.1242/jcs.127779

PubMed ID:

23843618

Uncontrolled Keywords:

Cytoskeleton, Intermediate filaments, Plakin, Plectin, Protein phosphorylation

BORIS DOI:

10.7892/boris.45602

URI:

https://boris.unibe.ch/id/eprint/45602

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