Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.2 (
PDK1
)
2,238
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hypotonic cell swelling in the myocardium is induced by pathological conditions, including ischemia-reperfusion, and affects the activities of ion transporters/channels and gene expression. However, the signaling mechanism activated by hypotonic stress (HS) is not fully understood in cardiac myocytes. A specialized protein kinase cascade, consisting of Pkc1 and MAPKs, is activated by HS in yeast. Here, we demonstrate that
protein kinase N1
(
PKN1
), a serine/threonine protein kinase and a homolog of Pkc1, is activated by HS (67% osmolarity) within 5 min and reaches peak activity at 60 min in cardiac myocytes. Activation of
PKN1
by HS was accompanied by Thr(774) phosphorylation and concomitant activation of
PDK1
, a potential upstream regulator of
PKN1
. HS also activated RhoA, thereby increasing interactions between
PKN1
and RhoA. PP1 (10(-5) M), a selective Src family tyrosine kinase inhibitor, significantly suppressed HS-induced activation of RhoA and
PKN1
. Constitutively active
PKN1
significantly increased the transcriptional activity of Elk1-GAL4, an effect that was inhibited by dominant negative MEK. Overexpression of
PKN1
significantly increased ERK phosphorylation, whereas downregulation of
PKN1
inhibited HS-induced ERK phosphorylation. Downregulation of
PKN1
and inhibition of ERK by U-0126 both significantly inhibited the survival of cardiac myocytes in the presence of HS. These results suggest that a signaling cascade, consisting of Src, RhoA,
PKN1
, and ERK, is activated by HS, thereby promoting cardiac myocyte survival.
...
PMID:Hypotonic swelling-induced activation of PKN1 mediates cell survival in cardiac myocytes. 2103 31
