Protein kinase X activates ureteric bud branching morphogenesis in developing mouse metanephric kidney

被引:18
作者
Li, XH [1 ]
Hyink, DP [1 ]
Polgar, K [1 ]
Gusella, GL [1 ]
Wilson, PD [1 ]
Burrow, CR [1 ]
机构
[1] CUNY Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2005年 / 16卷 / 12期
关键词
D O I
10.1681/ASN.2005030240
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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 is 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.
引用
收藏
页码:3543 / 3552
页数:10
相关论文
共 35 条
[1]   Integration of signaling networks that regulate Dictyostelium differentiation [J].
Aubry, L ;
Firtel, R .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1999, 15 :469-517
[2]   PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2 [J].
Bhunia, AK ;
Piontek, K ;
Boletta, A ;
Liu, LJ ;
Qian, F ;
Xu, PN ;
Germino, FJ ;
Germino, GG .
CELL, 2002, 109 (02) :157-168
[3]   A novel murine PKA-related protein kinase involved in neuronal differentiation [J].
Blaschke, RJ ;
Monaghan, AP ;
Bock, D ;
Rappold, GA .
GENOMICS, 2000, 64 (02) :187-194
[4]   Serine and threonine phosphorylation of the paxillin LIM domains regulates paxillin focal adhesion localization and cell adhesion to fibronectin [J].
Brown, MC ;
Perrotta, JA ;
Turner, CE .
MOLECULAR BIOLOGY OF THE CELL, 1998, 9 (07) :1803-1816
[5]  
CARY LA, 1999, FRONT BIOSCI, V4, P102
[6]   Modification of the composition of polycystin-1 multiprotein complexes by calcium and tyrosine phosphorylation [J].
Geng, L ;
Burrow, CR ;
Li, HP ;
Wilson, PD .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2000, 1535 (01) :21-35
[7]   Protein kinase a is a negative regulator of renal branching morphogenesis and modulates inhibitory and stimulatory bone morphogenetic proteins [J].
Gupta, IR ;
Piscione, TD ;
Grisaru, S ;
Phan, T ;
Macias-Silva, M ;
Zhou, XP ;
Whiteside, C ;
Wrana, JL ;
Rosenblum, ND .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (37) :26305-26314
[8]   Lentiviral gene transduction of kidney [J].
Gusella, GL ;
Fedorova, E ;
Hanss, B ;
Marras, D ;
Klotman, ME ;
Klotman, PE .
HUMAN GENE THERAPY, 2002, 13 (03) :407-414
[9]  
Huang TS, 1999, GENET MED, V1, P104
[10]   THE CATALYTIC SUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE FROM ASCARIS-SUUM - THE CLONING AND STRUCTURE OF A NOVEL SUBTYPE OF PROTEIN-KINASE-A [J].
JUNG, S ;
HOFFMANN, R ;
RODRIGUEZ, PH ;
MUTZEL, R ;
HOFER, HW .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1995, 232 (01) :111-117