Downregulation of Chloride Channel ClC-2 by Janus Kinase 3

Downregulation of Chloride Channel ClC-2 by Janus Kinase 3 Janus kinase-3 (JAK3) fosters proliferation and counteracts apoptosis of lymphocytes and tumor cells. The gain of function mutation A572VJAK3 has been discovered in acute megakaryoplastic leukemia. JAK3 is inactivated by replacement of lysine by alanine in the catalytic subunit (K855AJAK3). Regulation of cell proliferation and apoptosis involves altered activity of Cl− channels. The present study, thus, explored whether JAK3 modifies the function of the small conductance Cl− channel ClC-2. To this end, ClC-2 was expressed in Xenopus oocytes with or without wild-type JAK3, A568VJAK3 or K851AJAK3, and the Cl− channel activity determined by dual-electrode voltage clamp. Channel protein abundance in the cell membrane was determined utilizing chemiluminescence. As a result, expression of ClC-2 was followed by a marked increase of cell membrane conductance. The conductance was significantly decreased following coexpression of JAK3 or A568VJAK3, but not by coexpression of K851AJAK3. Exposure of the oocytes expressing ClC-2 together with A568VJAK3 to the JAK3 inhibitor WHI-P154 (4-[(3’-bromo-4’-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline, 22 μM) increased the conductance. Coexpression of A568VJAK3 decreased the ClC-2 protein abundance in the cell membrane of ClC-2 expressing oocytes. The decline of conductance in ClC-2 and A568VJAK3 coexpressing oocytes following inhibition of channel protein insertion by brefeldin A (5 μM) was similar in oocytes expressing ClC-2 with A568VJAK3 and oocytes expressing ClC-2 alone, indicating that A568VJAK3 might slow channel protein insertion into rather than accelerating channel protein retrieval from the cell membrane. In conclusion, JAK3 downregulates ClC-2 activity and thus counteracts Cl− exit—an effect possibly influencing cell proliferation and apoptosis. The Journal of Membrane Biology Springer Journals

Downregulation of Chloride Channel ClC-2 by Janus Kinase 3

Loading next page...
Springer US
Copyright © 2014 by Springer Science+Business Media New York
Life Sciences; Biochemistry, general; Human Physiology
Publisher site
See Article on Publisher Site


You’re reading a free preview. Subscribe to read the entire article.

DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches


Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.



billed annually
Start Free Trial

14-day Free Trial