Protein kinase X activates ureteric bud branching morphogenesis in developing mouse metanephric kidney.
The human protein kinase X (PRKX) gene was identified previously as a cAMP-dependent serine/threonine kinase that is aberrantly expressed in autosomal dominant polycystic disease kidneys and normally expressed in fetal kidneys. The PRKX kinase belongs to a serine/threonine kinase family that is phylogenetically and functionally distinct from classical protein kinase A kinases. Expression of PRKX activates cAMP-dependent renal epithelial cell migration and tubular morphogenesis in cell culture, suggesting that it might regulate branching growth of the collecting duct system in the fetal kidney. With the use of a mouse embryonic kidney organ culture system that recapitulates early kidney development in vitro, it is demonstrated that lentiviral vector-driven expression of a constitutively active, cAMP-independent PRKX in the ureteric bud epithelium stimulates branching morphogenesis and results in a 2.5-fold increase in glomerular number. These results suggest that PRKX stimulates epithelial branching morphogenesis by activating cell migration and support a role for this kinase in the regulation of nephrogenesis and of collecting system development in the fetal kidney.
Li
Xiaohong
X
Department of Medicine, Division of Nephrology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Hyink
Deborah P
DP
Polgar
Katalin
K
Gusella
G Luca
GL
Wilson
Patricia D
PD
Burrow
Christopher R
CR
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007668:Kidney / Q000196:embryology* / Q000473:pathology; D051379:Mice; D038081:Organogenesis / Q000235:genetics / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D014513:Ureter / Q000196:embryology* / Q000473:pathology
D012333:RNA, Messenger; D011494:Protein Kinases