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| Content Provider | PubMed Central |
|---|---|
| Author | Newton, Ryan H. Sabrina, Leverrier Srikanth, Sonal Gwack, Yousang Cahalan, Michael D. Walsh, Craig M. |
| Copyright Year | 2011 |
| Abstract | DRAK2 is a serine/threonine kinase highly enriched in lymphocytes that raises the threshold for T cell activation and maintains T cell survival following productive activation. T cells lacking DRAK2 are prone to activation under suboptimal conditions and exhibit enhanced calcium responses to AgR stimulation. Despite this, mice lacking DRAK2 are resistant to organ-specific autoimmune diseases due to defective autoreactive T cell survival. DRAK2 kinase activity is induced by AgR signaling, and in this study we show that the induction of DRAK2 activity requires Ca2+ influx through the Ca2+ release-activated Ca2+ channel formed from Orai1 subunits. Blockade of DRAK2 activity with the protein kinase D (PKD) inhibitor Gö6976 or expression of a kinase-dead PKD mutant prevented activation of DRAK2, whereas a constitutively active PKD mutant promoted DRAK2 function. Knockdown of PKD in T cells strongly blocked endogenous DRAK2 activation following TCR ligation, implicating PKD as an essential intermediate in the activation of DRAK2 by Ca2+ influx. Furthermore, we identify DRAK2 as a novel substrate of PKD, and demonstrate that DRAK2 and PKD physically interact under conditions that activate PKD. Mitochondrial generation of reactive oxygen intermediates was necessary and sufficient for DRAK2 activation in response to Ca2+ influx. Taken together, DRAK2 and PKD form a novel signaling module that controls calcium homeostasis following T cell activation. |
| Related Links | http://dx.doi.org/10.4049/jimmunol.1000942 |
| Starting Page | 940 |
| File Format | |
| ISSN | 15506606 |
| e-ISSN | 15506606 |
| Journal | Journal of immunology (Baltimore, Md. : 1950) |
| Issue Number | 2 |
| Volume Number | 186 |
| Language | English |
| Publisher Date | 2011-01-15 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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