Logo image
Back
Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation
Journal article   Open access   Peer reviewed

Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation

Yi Cai, Mark S Lechner, Deepak Nihalani, Marc J Prindle, Lawrence B Holzman, Gregory R Dressler and Yuanfang Cai
The Journal of biological chemistry, v 277(2), pp 1217-1222
11 Jan 2002
DOI: https://doi.org/10.1074/jbc.M109663200
PMID: 11700324
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1074/jbc.m109663200View
Published, Version of Record (VoR)CC BY V4.0,  Open
url
https://doi.org/10.1074/jbc.M109663200View
Published, Version of Record (VoR) Open

Abstract

Cell Line DNA-Binding Proteins - metabolism Genes, Reporter Humans JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases - metabolism PAX2 Transcription Factor Phosphorylation Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins - metabolism Recombinant Fusion Proteins - metabolism Signal Transduction Transcription Factors - metabolism Transcriptional Activation Transfection Wnt Proteins Zebrafish Proteins
The Pax gene family encodes DNA-binding proteins that can both activate and repress transcription of specific target genes during embryonic development. Pax proteins are required for pattern formation and cell differentiation in a broad spectrum of developing tissues. Consistent with its expression in the intermediate mesoderm, the optic cup and stalk, and the otic vesicle, Pax2, a member of the Pax2/5/8 subfamily, is essential for the development of the renal epithelia, the optic cup, and the inner ear. In addition to a DNA binding domain, the Pax2 protein contains a carboxyl-terminal transactivation domain rich in serine, threonine, and tyrosine. In this report, we demonstrate that the Pax2 transactivation domain is phosphorylated by the c-Jun N-terminal kinase, but not the ERK1/2 or p38 MAP kinases and that phosphorylation is coincident with increased transactivation of a Pax2-dependent reporter gene. Activation of JNK by either upstream kinase MEKK1 or DLK or by expression of Wnt signaling proteins significantly enhances Pax2 phosphorylation in cells. In vitro kinase assays using immunoprecipitated JNK or constitutively active, recombinant JNK show phosphorylation of GST-Pax2 fusion proteins. In transfected cells, phosphorylation of Pax2 correlates with increased transactivation of a Pax2-dependent reporter gene, suggesting that serine/threonine phosphorylation of the transactivation domain is important for Pax2 activity. Pax2 can form a complex with the JNK scaffolding protein JIP1, and this interaction is enhanced by activation of the JNK signaling module with the upstream kinase DLK. The data demonstrate that Pax2 is a new target for the JNK signaling module and point to a novel mechanism for mediating Pax-dependent transcription regulation.

Metrics

13 Record Views
76 citations in Web of Science
78 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Biochemistry & Molecular Biology
Logo image