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Protein kinase-X interacts with Pin-1 and Polycystin-1 during mouse kidney development

Xiaohong Li1, Deborah P Hyink, Brian Radbill

  • 1Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA. xiaohong.li@mssm.edu

Kidney International
|April 16, 2009
PubMed

Insights

Protein Kinase-X (PRKX) regulates kidney development by influencing cell migration and branching. PRKX interacts with Polycystin-1 and Pin-1, suggesting they mediate its function in epithelial morphogenesis.

Area of Science:

  • Nephrology
  • Developmental Biology
  • Molecular Biology

Background:

  • Bone morphogenetic protein-7 regulates epithelial branching morphogenesis via cyclic adenosine monophosphate (cAMP)-dependent protein kinases.
  • Protein Kinase-X (PRKX), a cAMP-dependent kinase, was previously identified as a regulator of epithelial morphogenesis and binds/phosphorylates Polycystin-1.

Purpose of the Study:

  • To determine the physiological functions of endogenous PRKX in kidney development.
  • To investigate the interactions of PRKX with other proteins in ureteric bud derivatives.

Main Methods:

  • Small interfering RNA (siRNA) mediated knockdown of PRKX gene expression in human fetal collecting tubule (HFCT) cells and embryonic mouse kidney explants.
  • Assessment of cell migration, adhesion, ureteric bud branching, and glomerular induction.
  • TransSignal domain arrays and co-immunoprecipitation assays to test for protein interactions.

Main Results:

  • PRKX knockdown (exceeding 70%) in HFCT cells decreased cell migration and increased cell adhesion to collagen I.
  • PRKX knockdown in embryonic mouse kidney explants reduced ureteric bud branching and glomerular induction.
  • PRKX was found to bind to BAG-3, PIN-1, and MAGI-1 via its WW domain and co-immunoprecipitated with Pin-1.

Conclusions:

  • Endogenous PRKX plays a crucial role in regulating renal epithelial cell migration, adhesion, and kidney development.
  • Polycystin-1 and Pin-1 are suggested to mediate the function of PRKX in kidney development through their interactions.

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