NEPH1 defines a novel family of podocin interacting proteins
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NEPH1 defines a novel family of podocin interacting proteins. / Sellin, Lorenz; Huber, Tobias B; Gerke, Peter; Quack, Ivo; Pavenstädt, Hermann; Walz, Gerd.
In: FASEB J, Vol. 17, No. 1, 01.2003, p. 115-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - NEPH1 defines a novel family of podocin interacting proteins
AU - Sellin, Lorenz
AU - Huber, Tobias B
AU - Gerke, Peter
AU - Quack, Ivo
AU - Pavenstädt, Hermann
AU - Walz, Gerd
PY - 2003/1
Y1 - 2003/1
N2 - Mutations of NPHS1 or NPHS2, the genes encoding for the glomerular podocyte proteins nephrin and podocin, cause steroid-resistant proteinuria. In addition, mice lacking NEPH1 develop a nephrotic syndrome that resembles NPHS mutations, suggesting that all three proteins are essential for the integrity of glomerular podocytes. Podocin interacts with the C-terminal domain of nephrin and facilitates nephrin-dependent signaling. NEPH1, a member of the immunoglobulin superfamily, is structurally related to nephrin. We report now that NEPH1 belongs to a family of three closely related proteins that interact with the C-terminal domain of podocin. All three NEPH proteins share a conserved podocin-binding motif; mutation of a centrally located tyrosine residue dramatically lowers the affinity of NEPH1 for podocin. NEPH1 triggers AP-1 activation similarly to nephrin but requires the presence of Tec family kinases for efficient transactivation. We conclude that NEPH1 defines a new family of podocin-binding molecules that are potential candidates for hereditary nephrotic syndromes not linked to either NPHS1 or NPHS2.
AB - Mutations of NPHS1 or NPHS2, the genes encoding for the glomerular podocyte proteins nephrin and podocin, cause steroid-resistant proteinuria. In addition, mice lacking NEPH1 develop a nephrotic syndrome that resembles NPHS mutations, suggesting that all three proteins are essential for the integrity of glomerular podocytes. Podocin interacts with the C-terminal domain of nephrin and facilitates nephrin-dependent signaling. NEPH1, a member of the immunoglobulin superfamily, is structurally related to nephrin. We report now that NEPH1 belongs to a family of three closely related proteins that interact with the C-terminal domain of podocin. All three NEPH proteins share a conserved podocin-binding motif; mutation of a centrally located tyrosine residue dramatically lowers the affinity of NEPH1 for podocin. NEPH1 triggers AP-1 activation similarly to nephrin but requires the presence of Tec family kinases for efficient transactivation. We conclude that NEPH1 defines a new family of podocin-binding molecules that are potential candidates for hereditary nephrotic syndromes not linked to either NPHS1 or NPHS2.
KW - Amino Acid Sequence
KW - Animals
KW - Carrier Proteins
KW - Cell Line
KW - Humans
KW - Intracellular Signaling Peptides and Proteins
KW - Kidney
KW - Membrane Proteins
KW - Mice
KW - Models, Biological
KW - Protein Structure, Tertiary
KW - Protein-Tyrosine Kinases
KW - Proteins
KW - Signal Transduction
KW - Transcription Factor AP-1
KW - Journal Article
U2 - 10.1096/fj.02-0242fje
DO - 10.1096/fj.02-0242fje
M3 - SCORING: Journal article
C2 - 12424224
VL - 17
SP - 115
EP - 117
JO - FASEB J
JF - FASEB J
SN - 0892-6638
IS - 1
ER -