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Vol. 27, No. 5, 2011
Issue release date: 2011
Section title: Original Paper
Cell Physiol Biochem 2011;27:547–556
(DOI:10.1159/000329956)

Janus Kinase 3 is Expressed in Erythrocytes, Phosphorylated Upon Energy Depletion and Involved in the Regulation of Suicidal Erythrocyte Death

Bhavsar S.K. · Gu S. · Bobbala D. · Lang F.
Department of Physiology, University of Tübingen, Tübingen

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Abstract

Janus kinase 3, a tyrosine kinase expressed in haematopoetic tissues, plays a decisive role in T-lymphocyte survival. JAK3 deficiency leads to (Severe) Combined Immunodeficiency (SCID) resulting from enhanced lymphocyte apoptosis. JAK3 is activated by phosphorylation. Nothing is known about expression of JAK3 in erythrocytes, which may undergo apoptosis-like cell death (eryptosis) characterized by cell membrane scrambling with phosphatidylserine exposure and cell shrinkage. Triggers of eryptosis include energy depletion. The present study utilized immunohistochemistry and confocal microscopy to test for JAK3 expression and phosphorylation, and FACS analysis to determine phosphatidylserine exposure (annexin binding) and cell volume (forward scatter). As a result, JAK3 was expressed in erythrocytes and phosphorylated following 24h and 48h glucose depletion. Forward scatter was slightly but significantly smaller in erythrocytes from JAK3-deficient mice (jak3-/-) than in erythrocytes from wild type mice (jak3+/+). Annexin V binding was similarly low in both genotypes. The JAK3 inhibitors WHI-P131/JANEX-1 (4-(4′-Hydroxyphenyl)amino-6,7-dimethoxyquinazoline, 156µM) and WHI-P154 (4-[(3′-Bromo-4′-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline, 11.2µM) did not significantly modify annexin V binding or forward scatter. Glucose depletion increased annexin V binding, an effect significantly blunted in jak3-/- erythrocytes and in the presence of the JAK3 inhibitors. The observations disclose a completely novel role of Janus kinase 3, i.e. the triggering of cell membrane scrambling in energy depleted erythrocytes.


  

Author Contacts

Prof. Dr. Florian Lang
Physiologisches Institut, der Universität Tübingen
Gmelinstr. 5, 72076 Tübingen (Germany)
Tel. +49 7071 29 72194, Fax +49 7071 29 5618
E-Mail florian.lang@uni-tuebingen.de

  

Article Information

Accepted: May 11, 2011
Published online: June 15, 2011
Number of Print Pages : 10

  

Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 27, No. 5, Year 2011 (Cover Date: 2011)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: 5/11/2011
Published online: 6/15/2011

Number of Print Pages: 0
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


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