Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein

N Geijsen; I J Uings; C Pals; J Armstrong; M McKinnon; J A Raaijmakers; J W Lammers; L Koenderman; P J Coffer

doi:10.1126/science.1059157

Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein

Science. 2001 Aug 10;293(5532):1136-8. doi: 10.1126/science.1059157.

Authors

N Geijsen¹, I J Uings, C Pals, J Armstrong, M McKinnon, J A Raaijmakers, J W Lammers, L Koenderman, P J Coffer

Affiliation

¹ Department of Pulmonary Diseases, Heart Lung Center Utrecht, University Medical Center, G03.550, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

PMID: 11498591
DOI: 10.1126/science.1059157

Abstract

Cytokine receptors consist of multiple subunits, which are often shared between different receptors, resulting in the functional redundancy sometimes observed between cytokines. The interleukin 5 (IL-5) receptor consists of an IL-5-specific alpha-subunit (IL-5Ralpha) and a signal-transducing beta-subunit (betac) shared with the IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors. In this study, we sought to find a role for the cytoplasmic domain of IL-5Ralpha. We show that syntenin, a protein containing PSD-95/Discs large/zO-1 (PDZ) domains, associates with the cytoplasmic tail of the IL-5Ralpha. Syntenin was found to directly associate with the transcription factor Sox4. Association of syntenin with IL-5Ralpha was required for IL-5-mediated activation of Sox4. These studies identify a mechanism of transcriptional activation by cytokine-specific receptor subunits.

MeSH terms

Animals
B-Lymphocytes / immunology
B-Lymphocytes / metabolism*
COS Cells
Carrier Proteins / chemistry
Carrier Proteins / metabolism*
Cell Line
Genes, Reporter
High Mobility Group Proteins / metabolism*
Humans
Interleukin-5 / pharmacology*
Intracellular Signaling Peptides and Proteins*
Membrane Proteins*
Mice
Mitogen-Activated Protein Kinases / metabolism
Phosphorylation
Point Mutation
Protein Structure, Tertiary
Receptors, Interleukin / chemistry
Receptors, Interleukin / genetics
Receptors, Interleukin / metabolism*
Receptors, Interleukin-5
Recombinant Fusion Proteins / metabolism
SOXC Transcription Factors
Sequence Deletion
Signal Transduction
Syntenins
Trans-Activators / metabolism*
Transcriptional Activation*
Transfection
Two-Hybrid System Techniques

Substances

Carrier Proteins
High Mobility Group Proteins
Interleukin-5
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Receptors, Interleukin
Receptors, Interleukin-5
Recombinant Fusion Proteins
SDCBP protein, human
SOX4 protein, human
SOXC Transcription Factors
Sox4 protein, mouse
Syntenins
Trans-Activators
Mitogen-Activated Protein Kinases