Bryostatin 1 Induces Biphasic Activation of Protein Kinase D in Intact Cells

Bryostatin 1 and phorbol esters are both potent activators of protein kinase C (PKC), although their specific biological effects can differ in many systems. Here, we report that bryostatin 1 activates protein kinase D (PKD), a novel serine/threonine protein kinase, in intact Swiss 3T3 cells and seco...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 1997-08, Vol.272 (32), p.20245-20250
Main Authors: Matthews, Sharon A., Pettit, George R., Rozengurt, Enrique
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Bryostatins
Dose-Response Relationship, Drug
Enzyme Activation - drug effects
Kinetics
Lactones - pharmacology
Macrolides
Mice
Mitogens - pharmacology
Phorbol 12,13-Dibutyrate - pharmacology
Phosphorylation
Protein Kinase C - metabolism
Protein-Serine-Threonine Kinases - metabolism
Tetradecanoylphorbol Acetate - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Bryostatin 1 and phorbol esters are both potent activators of protein kinase C (PKC), although their specific biological effects can differ in many systems. Here, we report that bryostatin 1 activates protein kinase D (PKD), a novel serine/threonine protein kinase, in intact Swiss 3T3 cells and secondary mouse embryo fibroblasts and in COS-7 cells transiently transfected with a PKD expression construct. The dose response of PKD activation induced by bryostatin 1 follows a striking biphasic pattern with maximal activation achieved at a concentration of 10 nm. Higher concentrations of bryostatin 1 (100 nm) reduced PKD activation induced by phorbol 12,13-dibutyrate to levels stimulated by bryostatin 1 alone. Bryostatin 1-induced PKD activation was markedly attenuated by treatment of cells with the PKC inhibitors bisindolylmaleimide I and Ro 31-8220. However, these agents did not inhibit PKD activity when added directly to in vitro kinase assays, suggesting that bryostatin 1 stimulates PKD activation through a PKC-dependent pathway in intact cells. Our results raise the possibility that activated PKD in intact cells could mediate some of the multiple biphasic biological responses induced by bryostatin 1.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.272.32.20245