NEPH1 defines a novel family of podocin interacting proteins.
FASEB J
; 17(1): 115-7, 2003 Jan.
Article
en En
| MEDLINE
| ID: mdl-12424224
ABSTRACT
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Alemania