Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein.
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.
Geijsen
N
N
Department of Pulmonary Diseases, Heart Lung Center Utrecht, University Medical Center, G03.550, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Uings
I J
IJ
Pals
C
C
Armstrong
J
J
McKinnon
M
M
Raaijmakers
J A
JA
Lammers
J W
JW
Koenderman
L
L
Coffer
P J
PJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D017930:Genes, Reporter; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053649:Receptors, Interleukin-5; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D055751:SOXC Transcription Factors; D017384:Sequence Deletion; D015398:Signal Transduction; D053676:Syntenins; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D006609:High Mobility Group Proteins; D015848:Interleukin-5; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D011993:Recombinant Fusion Proteins; C109621:SDCBP protein, human; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D053676:Syntenins; D015534:Trans-Activators; D020928:Mitogen-Activated Protein Kinases