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Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling

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Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. / Huber, Tobias B; Hartleben, Björn; Kim, Jeong; Schmidts, Miriam; Schermer, Bernhard; Keil, Alexander; Egger, Lotti; Lecha, Rachel L; Borner, Christoph; Pavenstädt, Hermann; Shaw, Andrey S; Walz, Gerd; Benzing, Thomas.

in: MOL CELL BIOL, Jahrgang 23, Nr. 14, 07.2003, S. 4917-28.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Huber, TB, Hartleben, B, Kim, J, Schmidts, M, Schermer, B, Keil, A, Egger, L, Lecha, RL, Borner, C, Pavenstädt, H, Shaw, AS, Walz, G & Benzing, T 2003, 'Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling', MOL CELL BIOL, Jg. 23, Nr. 14, S. 4917-28.

APA

Huber, T. B., Hartleben, B., Kim, J., Schmidts, M., Schermer, B., Keil, A., Egger, L., Lecha, R. L., Borner, C., Pavenstädt, H., Shaw, A. S., Walz, G., & Benzing, T. (2003). Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. MOL CELL BIOL, 23(14), 4917-28.

Vancouver

Huber TB, Hartleben B, Kim J, Schmidts M, Schermer B, Keil A et al. Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. MOL CELL BIOL. 2003 Jul;23(14):4917-28.

Bibtex

@article{0225782defca44118fb07a3254ae2c62,
title = "Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling",
abstract = "Mutations of NPHS1 or NPHS2, the genes encoding nephrin and podocin, as well as the targeted disruption of CD2-associated protein (CD2AP), lead to heavy proteinuria, suggesting that all three proteins are essential for the integrity of glomerular podocytes, the visceral glomerular epithelial cells of the kidney. It has been speculated that these proteins participate in common signaling pathways; however, it has remained unclear which signaling proteins are actually recruited by the slit diaphragm protein complex in vivo. We demonstrate that both nephrin and CD2AP interact with the p85 regulatory subunit of phosphoinositide 3-OH kinase (PI3K) in vivo, recruit PI3K to the plasma membrane, and, together with podocin, stimulate PI3K-dependent AKT signaling in podocytes. Using two-dimensional gel analysis in combination with a phosphoserine-specific antiserum, we demonstrate that the nephrin-induced AKT mediates phosphorylation of several target proteins in podocytes. One such target is Bad; its phosphorylation and inactivation by 14-3-3 protects podocytes against detachment-induced cell death, suggesting that the nephrin-CD2AP-mediated AKT activity can regulate complex biological programs. Our findings reveal a novel role for the slit diaphragm proteins nephrin, CD2AP, and podocin and demonstrate that these three proteins, in addition to their structural functions, initiate PI3K/AKT-dependent signal transduction in glomerular podocytes.",
keywords = "14-3-3 Proteins, Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Cell Line, Cell Membrane, Cytoskeletal Proteins, Dogs, Humans, Intracellular Signaling Peptides and Proteins, Kidney, Membrane Proteins, Mice, Phosphatidylinositol 3-Kinases, Phosphorylation, Protein Subunits, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Signal Transduction, Tyrosine 3-Monooxygenase, bcl-Associated Death Protein, Journal Article, Research Support, Non-U.S. Gov't",
author = "Huber, {Tobias B} and Bj{\"o}rn Hartleben and Jeong Kim and Miriam Schmidts and Bernhard Schermer and Alexander Keil and Lotti Egger and Lecha, {Rachel L} and Christoph Borner and Hermann Pavenst{\"a}dt and Shaw, {Andrey S} and Gerd Walz and Thomas Benzing",
year = "2003",
month = jul,
language = "English",
volume = "23",
pages = "4917--28",
journal = "MOL CELL BIOL",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "14",

}

RIS

TY - JOUR

T1 - Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling

AU - Huber, Tobias B

AU - Hartleben, Björn

AU - Kim, Jeong

AU - Schmidts, Miriam

AU - Schermer, Bernhard

AU - Keil, Alexander

AU - Egger, Lotti

AU - Lecha, Rachel L

AU - Borner, Christoph

AU - Pavenstädt, Hermann

AU - Shaw, Andrey S

AU - Walz, Gerd

AU - Benzing, Thomas

PY - 2003/7

Y1 - 2003/7

N2 - Mutations of NPHS1 or NPHS2, the genes encoding nephrin and podocin, as well as the targeted disruption of CD2-associated protein (CD2AP), lead to heavy proteinuria, suggesting that all three proteins are essential for the integrity of glomerular podocytes, the visceral glomerular epithelial cells of the kidney. It has been speculated that these proteins participate in common signaling pathways; however, it has remained unclear which signaling proteins are actually recruited by the slit diaphragm protein complex in vivo. We demonstrate that both nephrin and CD2AP interact with the p85 regulatory subunit of phosphoinositide 3-OH kinase (PI3K) in vivo, recruit PI3K to the plasma membrane, and, together with podocin, stimulate PI3K-dependent AKT signaling in podocytes. Using two-dimensional gel analysis in combination with a phosphoserine-specific antiserum, we demonstrate that the nephrin-induced AKT mediates phosphorylation of several target proteins in podocytes. One such target is Bad; its phosphorylation and inactivation by 14-3-3 protects podocytes against detachment-induced cell death, suggesting that the nephrin-CD2AP-mediated AKT activity can regulate complex biological programs. Our findings reveal a novel role for the slit diaphragm proteins nephrin, CD2AP, and podocin and demonstrate that these three proteins, in addition to their structural functions, initiate PI3K/AKT-dependent signal transduction in glomerular podocytes.

AB - Mutations of NPHS1 or NPHS2, the genes encoding nephrin and podocin, as well as the targeted disruption of CD2-associated protein (CD2AP), lead to heavy proteinuria, suggesting that all three proteins are essential for the integrity of glomerular podocytes, the visceral glomerular epithelial cells of the kidney. It has been speculated that these proteins participate in common signaling pathways; however, it has remained unclear which signaling proteins are actually recruited by the slit diaphragm protein complex in vivo. We demonstrate that both nephrin and CD2AP interact with the p85 regulatory subunit of phosphoinositide 3-OH kinase (PI3K) in vivo, recruit PI3K to the plasma membrane, and, together with podocin, stimulate PI3K-dependent AKT signaling in podocytes. Using two-dimensional gel analysis in combination with a phosphoserine-specific antiserum, we demonstrate that the nephrin-induced AKT mediates phosphorylation of several target proteins in podocytes. One such target is Bad; its phosphorylation and inactivation by 14-3-3 protects podocytes against detachment-induced cell death, suggesting that the nephrin-CD2AP-mediated AKT activity can regulate complex biological programs. Our findings reveal a novel role for the slit diaphragm proteins nephrin, CD2AP, and podocin and demonstrate that these three proteins, in addition to their structural functions, initiate PI3K/AKT-dependent signal transduction in glomerular podocytes.

KW - 14-3-3 Proteins

KW - Adaptor Proteins, Signal Transducing

KW - Animals

KW - Carrier Proteins

KW - Cell Line

KW - Cell Membrane

KW - Cytoskeletal Proteins

KW - Dogs

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Kidney

KW - Membrane Proteins

KW - Mice

KW - Phosphatidylinositol 3-Kinases

KW - Phosphorylation

KW - Protein Subunits

KW - Protein-Serine-Threonine Kinases

KW - Proteins

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins c-akt

KW - Signal Transduction

KW - Tyrosine 3-Monooxygenase

KW - bcl-Associated Death Protein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - SCORING: Journal article

C2 - 12832477

VL - 23

SP - 4917

EP - 4928

JO - MOL CELL BIOL

JF - MOL CELL BIOL

SN - 0270-7306

IS - 14

ER -