Pasteurella multocida Toxin-induced Pim-1 expression disrupts suppressor of cytokine signalling (SOCS)-1 activity

Cellular Microbiology
Dagmar HildebrandKatharina F Kubatzky

Abstract

Pasteurella multocida Toxin (PMT) is a mitogenic protein toxin that manipulates signal transduction cascades of mammalian host cells and upregulates Janus kinase (JAK) and signal transducers of transcription (STAT) activity. Here we show that in the presence of PMT, increased levels of suppressors of cytokine signalling-1 (SOCS-1) proteins significantly enhance STAT activity. This occurs via PMT-induced expression of the serine/threonine kinase Pim-1 and subsequent threonine phosphorylation of SOCS-1. The ability of SOCS-1 to act as an E3 ubiquitin ligase is regulated by its phosphorylation status. Thus, the tyrosine kinase JAK2 cannot be marked for proteasomal degradation by threonine phosphorylated SOCS-1. Consequently, the expression levels of JAK2 are increased, eventually leading to hyperactivity of JAK2 and its target, the transcription factor STAT3. Eventually this causes increased anchorage-independent cell growth that correlates with the expression levels of SOCS-1. Interestingly, endogenous SOCS-1 production after Toll-like receptor activation also causes STAT3 hyperactivation. Thus we hypothesize that P. multocida Toxin alters host cell signalling using mechanisms that have so far only been known to be employed by on...Continue Reading

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Citations

Nov 15, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joachim H C OrthKlaus Aktories
Sep 26, 2013·Toxins·Katharina F KubatzkyDagmar Hildebrand
Jul 5, 2013·Clinical Microbiology Reviews·Brenda A Wilson, Mengfei Ho
Dec 12, 2012·Veterinary Immunology and Immunopathology·Mario Delgado-OrtegaFrançois Meurens
Dec 5, 2015·Frontiers in Microbiology·Dagmar HildebrandKatharina F Kubatzky
Dec 2, 2014·Cell Reports·Dagmar HildebrandKatharina F Kubatzky
Nov 1, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amber M PaulFengwei Bai
Nov 6, 2015·Frontiers in Microbiology·Aline SährKlaus Heeg

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