These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Ca(2+)/calmodulin-dependent protein kinase II inhibition by heparin in mesangial cells.
    Author: Xiao W, Liu Y, Templeton DM.
    Journal: Am J Physiol Renal Physiol; 2005 Jan; 288(1):F142-9. PubMed ID: 15383398.
    Abstract:
    Heparin exerts an antiproliferative effect in smooth muscle cells, and the Ca(2+)/calmodulin-dependent protein kinase (CaMK) signaling pathway is heparin sensitive. Here, we report that transfection with a truncated 326-amino acid fragment of CaMK-IIalpha increases basal activity of CaMK-II in mesangial cells. Ionomycin increased CaMK-II activity in both transfected and untransfected cells, with a concomitant increase in activated Ca(2+)/calmodulin. Heparin (1 microg/ml), but not chondroitin or dermatan sulfate, significantly attenuated both serum- or ionomycin-induced CaMK-II activity, and attendant c-fos mRNA expression, but did not affect upstream Ca(2+)/calmodulin. Autophosphorylation of Thr286 generates an autonomously active CaMK-II. Both serum and ionomycin increased phosphorylation at this site and increased CaMK-II activity in antiphosphothreonine immunoprecipitates. Heparin (1 microg/ml) did not inhibit phosphorylation of Thr286 (although much higher concentrations did). Replacement of Thr286 with Asp produces a constitutively active mutant that was insensitive to ionomycin but was inhibited by heparin maximally at 1 microg/ml. These results suggest that heparin at physiological concentrations acts at or downstream of CaMK-II to suppress its activity independent of an effect on autophosphorylation.
    [Abstract] [Full Text] [Related] [New Search]