ID: 204. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Siegmund, Samadhi Aparicio; Sommer, Jan; Scheller, Jürgen; Rose-John, Stefan; Garbers, Christoph
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 101
• Page End: 102
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.208
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">Cytokines of the Interleukin (IL)-6-family have essential functions in the control of inflammatory responses and immune defense. All members signal through the <inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7ntj" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e96" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula>-receptor gp130, albeit they activate different homo- and heterodimeric receptor complexes. Complex formation results in activation of the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway which is known to play an important role in diseases including autoimmunity and cancer, making a stringent regulation necessary.</p> <p id="sp010">The Protein kinase II (CK2) is a constitutively active serine/threonine kinase that regulates proliferation through diverse interactions with many signaling pathways and that is shown to be overexpressed in various cancer types including hematopoietic tumors.</p> <p id="sp015">We show that STAT1 and STAT3 activation by IL-6 and all other family members is abolished by CK2 inhibition. Furthermore, cytokine independent Jak/STAT activation via an activating deletion mutation in domain 2 of gp130 (gp130<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7k8p" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si2.gif" display="inline" overflow="scroll" id="d13e105" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">Δ</mml:mi></mml:mrow></mml:math></alternatives></inline-formula>YY) is critically dependent on the activity of both CK2 and Jak1. An activating mutation in STAT3 that was found in large granular lymphocytic leukemia (STAT3 Y640F) leads to constitutive STAT3 phosphorylation, which could be blocked via pharmacological inhibition of CK2. We furthermore confirmed the dominant role of Jak1 and not Jak2 for cytokine induced and constitutive STAT signaling with the help of different murine embryonic fibroblasts (MEFs).</p> <p id="sp020">In summary, we show a novel link between the Jak/STAT signaling pathway and the activity of the protein kinase CK2.</p> </sec> </abstract>