| First Author | Sellin L | Year | 2003 |
| Journal | FASEB J | Volume | 17 |
| Issue | 1 | Pages | 115-7 |
| PubMed ID | 12424224 | Mgi Jnum | J:385590 |
| Mgi Id | MGI:8343493 | Doi | 10.1096/fj.02-0242fje |
| Citation | Sellin L, et al. (2003) NEPH1 defines a novel family of podocin interacting proteins. FASEB J 17(1):115-7 |
| abstractText | 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. |
