A role for prolyl isomerase PIN1 in the phosphorylation- dependent modulation of PRRXL1 function

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Ricardo Soares dos Reis (Author) FMUP; Pessoa, AS (Author) Other; Dias, AF (Author) Other; Falcao, M (Author) Other; Matos, MR (Author) Other; Vitorino, R (Author) FMUP; Filipe Monteiro (Author) FMUP; Lima, D (Author) Other; reguenga, c (Author) FMUP

Journal

Title: Biochemical Journal

Vol. 474

Pages: 683-697

ISSN: 0264-6021

Publisher: PORTLAND PRESS LTD

Indexing

ISI Web of Knowledge - 0 Citations

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Other information

Authenticus ID: P-00M-HRN

DOI: 10.1042/bcj20160560

Abstract (EN): Prrxl1 encodes for a paired-like homeodomain transcription factor essential for the correct establishment of the dorsal root ganglion - spinal cord nociceptive circuitry during development. Prrxl1-null mice display gross anatomical disruption of this circuitry, which translates to a markedly diminished sensitivity to noxious stimuli. Here, by the use of an immunoprecipitation and mass spectrometry approach, we identify five highly conserved phosphorylation sites (T110, S119, S231, S233 and S251) in PRRXL1 primary structure. Four are phospho-S/T-P sites, which suggest a role for the prolyl isomerase PIN1 in regulating PRRXL1. Accordingly, PRRXL1 physically interacts with PIN1 and displays diminished transcriptional activity in a Pin1-null cell line. Additionally, these S/T-P sites seem to be important for PRRXL1 conformation, and their point mutation to alanine or aspartate down- regulates PRRXL1 transcriptional activity. Altogether, our findings provide evidence for a putative novel role of PIN1 in the development of the nociceptive system and indicate phosphorylation-mediated conformational changes as a mechanism for regulating the PRRXL1 role in the process.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15