HA1004, an inhibitor of serine/threonine protein kinases, restores the sensitivity of thymic lymphomas to Ca super(2+)-mediated apoptosis through a protein kinase A-independent mechanism

Our previous reports showed that thymic lymphomas arising in TCR transgenic mice are resistant to Ca super(2+)-mediated apoptosis. Here we show that induction of apoptosis in thymic lymphomas involves a process that is cAMP-mediated and which depends on the activation of protein kinase A (PKA) despi...

Full description

Saved in:
Bibliographic Details
Published in:International immunopharmacology 2002-03, Vol.2 (4), p.435-442
Main Authors: Matuszyk, J, Cebrat, M, Kalas, W, Strzadala, L
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Our previous reports showed that thymic lymphomas arising in TCR transgenic mice are resistant to Ca super(2+)-mediated apoptosis. Here we show that induction of apoptosis in thymic lymphomas involves a process that is cAMP-mediated and which depends on the activation of protein kinase A (PKA) despite the lower level of PKA type I in these lymphomas compared to thymocytes. Further, we show that treatment of the lymphomas with HA1004, a serine/threonine protein kinase inhibitor, restores their susceptibility to ionomycin-induced apoptosis. Results indicate that HA1004-induced restoration of sensitivity to ionomycin proceeds through a PKA-independent mechanism. Moreover, activation of PKA instead of its inhibition induces apoptosis of lymphoma cells.
ISSN:1567-5769