Ser(119) phosphorylation modulates the activity and conformation of PRRXL1, a homeodomain transcription factor

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Ricardo Reis (Author) FMUP; Ana Pessoa (Author) FMUP; Mariana Matos (Author) FMUP; Miguel Falcão (Author) FMUP; Filipe Monteiro (Author) FMUP; Deolinda Lima (Author) FMUP; Carlos Reguenga (Author) FMUP

Journal

Title: Biochemical Journal

Vol. 459

Pages: 441-453

ISSN: 0264-6021

Publisher: PORTLAND PRESS LTD

Indexing

ISI Web of Knowledge - 7 Citations

ISI Web of Science

Scopus - 7 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Health sciences

CORDIS: Natural sciences > Biological sciences > Biology > Developmental biology ; Natural sciences > Biological sciences > Biology > Molecular biology ; Health sciences > Neuroscience > Neurobiology

Other information

Authenticus ID: P-009-C3J

DOI: 10.1042/bj20131014

Abstract (EN): PRRXL1 [paired related homeobox-like 1; also known as DRG11 (dorsal root ganglia 11)] is a paired-like homeodomain transcription factor expressed in DRG and dSC (dorsal spinal cord) nociceptive neurons. PRRXL1 is crucial for the establishment and maintenance of nociceptive circuitry, as Prrxl1(-/-) mice present neuronal loss, reduced pain sensitivity and failure to thrive. In the present study, we show that PRRXL1 is highly phosphorylated in vivo, and that its multiple band pattern on electrophoretic analysis is the result of different phosphorylation states. PRRXL1 phosphorylation appears to be differentially regulated along the dSC and DRG development and it is mapped to two functional domains. One region comprises amino acids 107-143, whereas the other one encompasses amino acids 227-263 and displays repressor activity. Using an immunoprecipitation MS approach, two phosphorylation sites were identified, Ser(119) and Ser(238). Phosphorylation at Ser(119) is shown to be determinant for PRRXL1 conformation and transcriptional activity. Ser(119) phosphorylation is thus proposed as a mechanism for regulating PRRXL1 function and conformation during nociceptive system development.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13