Renal expression and activity of the germinal center kinase SK2.
Rat fetal kidney mRNA was analyzed by RT-PCR to identify protein kinases. This screening demonstrated expression of a protein kinase consistent with SK2, a group II germinal center kinase and homolog of human Ste20-like kinase (SLK). SK2 mRNA, protein expression, and kinase activity were increased in rat fetal kidney homogenates (embryonic days 17-21) compared with adult controls. In adult kidneys subjected to cross-clamping of the renal artery, followed by reperfusion, SK2 mRNA, protein expression, and kinase activity were increased compared with untreated contralateral controls. By immunohistochemistry, SK2 expression was evident mainly in the cytoplasm of tubular epithelial cells in fetal and adult kidneys. There was also some expression in developing and mature podocytes, but staining of the interstitium was negative. In cultured renal tubular epithelial cells, SK2 kinase activity was increased after incubation with serum, or after exposure to chemical anoxia plus reexposure to glucose. Stable overexpression of SLK reduced cell proliferation and increased apoptosis and exacerbated apoptosis and necrosis after chemical anoxia plus reexposure to glucose. Thus SK2 is a renal epithelial protein kinase whose expression and activity are increased during development and recovery from acute renal failure, where tubular epithelial regeneration may recapitulate developmental processes. The actions of SK2 appear to be antiproliferative and may facilitate cell injury.
Cybulsky
Andrey V
AV
Division of Nephrology, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1. andrey.cybulsky@mcgill.ca
Takano
Tomoko
T
Papillon
Joan
J
Khadir
Abdelkrim
A
Bijian
Krikor
K
Chien
Chu-Chun
CC
Alpers
Charles E
CE
Rabb
Hamid
H
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D000081410:Germinal Center Kinases; D007668:Kidney / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015398:Signal Transduction; D000099317:Hippo Kinases
D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; C485733:SLK protein, human; D000099317:Hippo Kinases; C481222:Slk protein, rat