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

Xiaohong Li; Deborah P. Hyink; Brian Radbill; Marius Sudol; Haojiang Zhang; Nadezda N. Zheleznova; Patricia D. Wilson

doi:10.1038/ki.2009.95

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

Xiaohong Li, Deborah P. Hyink, Brian Radbill, Marius Sudol, Haojiang Zhang, Nadezda N. Zheleznova, Patricia D. Wilson

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

The regulation of epithelial branching morphogenesis by bone morphogenetic protein-7 depends, in part, on functionally defined cyclic adenosine monophosphate (cAMP)-dependent protein kinases. We previously identified protein kinase-X (PRKX), a cAMP-dependent kinase, as a regulator of epithelial morphogenesis during kidney development and found that it binds to and phosphorylates Polycystin-1. Overexpression of PRKX stimulates renal epithelial cell migration, tubulogenesis, ureteric bud branching, and glomerular induction in embryonic mouse kidney explants in organ cultures. Here we determined the physiological functions of endogenous PRKX. Knockdown by siRNA of PRKX gene expression in a human fetal collecting tubule (HFCT) cell line exceeded 70% and resulted in decreased cell migration and increased adhesion of the cells to a collagen I matrix. In embryonic mouse kidney explants, the same degree of knockdown decreased ureteric bud branching and glomerular induction. Because PRKX BAG-3 PIN-1 and MAGI-1 are all expressed in ureteric bud derivatives, we tested for interactions among them and found that PRKX binds to all three proteins through its WW domain as determined by TransSignal domain arrays, and it coimmunoprecipitated with Pin-1 in HFCT cell lysates. These studies suggest that Polycystin-1 and Pin-1 may mediate the function of PRKX in kidney development.

Original language	English
Pages (from-to)	54-62
Number of pages	9
Journal	Kidney International
Volume	76
Issue number	1
DOIs	https://doi.org/10.1038/ki.2009.95
State	Published - Jul 2009

Keywords

Adhesion
Cyclic AMP
Migration
Morphogenesis
Renal developmental biology

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10.1038/ki.2009.95

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title = "Protein kinase-X interacts with Pin-1 and Polycystin-1 during mouse kidney development",

abstract = "The regulation of epithelial branching morphogenesis by bone morphogenetic protein-7 depends, in part, on functionally defined cyclic adenosine monophosphate (cAMP)-dependent protein kinases. We previously identified protein kinase-X (PRKX), a cAMP-dependent kinase, as a regulator of epithelial morphogenesis during kidney development and found that it binds to and phosphorylates Polycystin-1. Overexpression of PRKX stimulates renal epithelial cell migration, tubulogenesis, ureteric bud branching, and glomerular induction in embryonic mouse kidney explants in organ cultures. Here we determined the physiological functions of endogenous PRKX. Knockdown by siRNA of PRKX gene expression in a human fetal collecting tubule (HFCT) cell line exceeded 70% and resulted in decreased cell migration and increased adhesion of the cells to a collagen I matrix. In embryonic mouse kidney explants, the same degree of knockdown decreased ureteric bud branching and glomerular induction. Because PRKX BAG-3 PIN-1 and MAGI-1 are all expressed in ureteric bud derivatives, we tested for interactions among them and found that PRKX binds to all three proteins through its WW domain as determined by TransSignal domain arrays, and it coimmunoprecipitated with Pin-1 in HFCT cell lysates. These studies suggest that Polycystin-1 and Pin-1 may mediate the function of PRKX in kidney development.",

keywords = "Adhesion, Cyclic AMP, Migration, Morphogenesis, Renal developmental biology",

author = "Xiaohong Li and Hyink, {Deborah P.} and Brian Radbill and Marius Sudol and Haojiang Zhang and Zheleznova, {Nadezda N.} and Wilson, {Patricia D.}",

note = "Funding Information: This work was supported by NIH P01 DK 62345 (PW). The MSSM Microscopy Shared Research Facility was supported in part by a Howard Hughes Medical Institute Biomedical Research Support Program award and an NIH-NCI shared resources Grant (R24 CA095823-01). We thank T. Nelson for technical assistance and Dr Andrew Chan for the kind offer of MAGI-1 antibody.",

year = "2009",

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AU - Li, Xiaohong

AU - Hyink, Deborah P.

AU - Radbill, Brian

AU - Sudol, Marius

AU - Zhang, Haojiang

AU - Zheleznova, Nadezda N.

AU - Wilson, Patricia D.

N1 - Funding Information: This work was supported by NIH P01 DK 62345 (PW). The MSSM Microscopy Shared Research Facility was supported in part by a Howard Hughes Medical Institute Biomedical Research Support Program award and an NIH-NCI shared resources Grant (R24 CA095823-01). We thank T. Nelson for technical assistance and Dr Andrew Chan for the kind offer of MAGI-1 antibody.

PY - 2009/7

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N2 - The regulation of epithelial branching morphogenesis by bone morphogenetic protein-7 depends, in part, on functionally defined cyclic adenosine monophosphate (cAMP)-dependent protein kinases. We previously identified protein kinase-X (PRKX), a cAMP-dependent kinase, as a regulator of epithelial morphogenesis during kidney development and found that it binds to and phosphorylates Polycystin-1. Overexpression of PRKX stimulates renal epithelial cell migration, tubulogenesis, ureteric bud branching, and glomerular induction in embryonic mouse kidney explants in organ cultures. Here we determined the physiological functions of endogenous PRKX. Knockdown by siRNA of PRKX gene expression in a human fetal collecting tubule (HFCT) cell line exceeded 70% and resulted in decreased cell migration and increased adhesion of the cells to a collagen I matrix. In embryonic mouse kidney explants, the same degree of knockdown decreased ureteric bud branching and glomerular induction. Because PRKX BAG-3 PIN-1 and MAGI-1 are all expressed in ureteric bud derivatives, we tested for interactions among them and found that PRKX binds to all three proteins through its WW domain as determined by TransSignal domain arrays, and it coimmunoprecipitated with Pin-1 in HFCT cell lysates. These studies suggest that Polycystin-1 and Pin-1 may mediate the function of PRKX in kidney development.

AB - The regulation of epithelial branching morphogenesis by bone morphogenetic protein-7 depends, in part, on functionally defined cyclic adenosine monophosphate (cAMP)-dependent protein kinases. We previously identified protein kinase-X (PRKX), a cAMP-dependent kinase, as a regulator of epithelial morphogenesis during kidney development and found that it binds to and phosphorylates Polycystin-1. Overexpression of PRKX stimulates renal epithelial cell migration, tubulogenesis, ureteric bud branching, and glomerular induction in embryonic mouse kidney explants in organ cultures. Here we determined the physiological functions of endogenous PRKX. Knockdown by siRNA of PRKX gene expression in a human fetal collecting tubule (HFCT) cell line exceeded 70% and resulted in decreased cell migration and increased adhesion of the cells to a collagen I matrix. In embryonic mouse kidney explants, the same degree of knockdown decreased ureteric bud branching and glomerular induction. Because PRKX BAG-3 PIN-1 and MAGI-1 are all expressed in ureteric bud derivatives, we tested for interactions among them and found that PRKX binds to all three proteins through its WW domain as determined by TransSignal domain arrays, and it coimmunoprecipitated with Pin-1 in HFCT cell lysates. These studies suggest that Polycystin-1 and Pin-1 may mediate the function of PRKX in kidney development.

KW - Adhesion

KW - Cyclic AMP

KW - Migration

KW - Morphogenesis

KW - Renal developmental biology

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SP - 54

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JO - Kidney International

JF - Kidney International

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ER -

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

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Keywords

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