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A novel role for the adaptor molecule CD2-associated protein in transforming growth factor-beta-induced apoptosis


, : A novel role for the adaptor molecule CD2-associated protein in transforming growth factor-beta-induced apoptosis. Journal of Biological Chemistry 279(35): 37004-37012

CD2-associated protein (CD2AP) is an adaptor molecule involved in T cell receptor signaling and podocyte homeostasis. CD2AP-deficient mice develop nephrotic syndrome and renal failure caused by glomerulosclerosis. Here we report that increased transforming growth factor-beta1 (TGF-beta1) expression and apoptosis were present in podocytes at the onset of albuminuria and were followed by depletion of podocytes associated with progressive focal-segmental glomerulosclerosis in CD2AP-/- mice. Conditionally immortalized podocytes derived from CD2AP-/- mice were more susceptible to TGF-beta-induced apoptosis compared with CD2AP+/+ podocytes. Reconstitution of CD2AP rescued CD2AP-/- podocytes from TGF-beta-induced apoptosis. CD2AP was required for early activation of anti-apoptotic phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase 1/2 by TGF-beta. In contrast, activation of pro-apoptotic p38 MAPK by TGF-beta was accelerated and enhanced in the absence of CD2AP. CD2AP was not required for PI3K/AKT activation by insulin and epidermal growth factor, indicating that CD2AP is a selective mediator of anti-apoptotic TGF-beta signaling. In summary, we identified CD2AP as a novel mediator for selective activation of survival pathways and repression of apoptosis signaling by TGF-beta in podocytes. Together, our in vitro and in vivo findings suggest that TGF-beta-induced podocyte apoptosis is an early pathomechanism in mice developing focal-segmental glomerulosclerosis associated with functional impairment of CD2AP.

US$19.90

PMID: 15213232

DOI: 10.1074/jbc.M403534200


Other references

Baglia, F.A.; Jameson, B.A.; Walsh, P.N., 1991: Identification and chemical synthesis of a substrate-binding site for factor IX on coagulation factor XIa. We have previously used monoclonal antibodies to identify an epitope on the heavy chain of factor XIa that is a substrate-binding site for factor IX (Sinha, D., Seaman, F.S., and Walsh, P.N. (1987) Biochemistry 26, 3768-3775; Baglia, F.A., Sinha,...

Ikuta, H., 1984: Strength and stiffness of wooden joints having an angle of 120 degrees fabricated by finger jointing. The strength of such joints was improved by using inserts of katsura [Cercidiphyllum japonicum] wood or of a cross-laminated block of 5 ezomatsu [Picea jezoensis] layers.

Battin, M.P., 2008: Terminal sedation: pulling the sheet over our eyes. Hastings Center Report 38(5): 27-30

Nadal, J.W., 1959: Cancer of the thyroid; a twenty-year follow-up. American Journal of Surgery 98(2): 190-195

Koteja J.; Lagowska B., 1986: Dysmicoccus balticus new species homoptera coccinea pseudococcidae. Dysmicoccus balticus sp. n. is close to D. walkeri (Newstead), but is distinct in the number and distribution of cerarii (C1, C3, C17, C18) differentiation of tubular ducts, distribution of multilocular pores, and others. It lives on leaf blades o...

Ishida Keisuke, 1977: Discovery of the Silurian limestone in the southwestern part of the Sakashu District, Tokushima Prefecture, Shikoku. Chishitsugaku Zasshi = Journal of the Geological Society of Japan 83(7): 437-438

Torbay, N.; Bracco, E.F.; Geliebter, A.; Stewart, I.M.; Hashim, S.A., 1985: Insulin increases body fat despite control of food intake and physical activity. The effect of experimentally induced hyperinsulinemia on body composition was studied in rats with food intakes precisely controlled by intragastric feeding and physical activity manipulated by sedation with chlordiazepoxide (CDP). Male Sprague-Da...

Bond V.P., 1970: Symposium on hemopoietic cellular proliferation section on the relationship of bone marrow structure to hemopoiesis and myelo proliferative syndromes boston massachusetts usa november 5 6 1969. Stohlman, Frederick, Jred By . Symposium On Hemopoietic Cellular Proliferation. Xii: New York, N.y., U.s.a.; London, England. 56-96

Kim, J.Young.; Lee, J., 2016: Considerations in performing open surgical excision of dorsal wrist ganglion cysts. To investigate which conditions should be considered to make a successful resection of the entire ganglion complex during open excision. We reviewed 52 patients who underwent open surgical excision of dorsal wrist ganglions. The inclusion criterio...

Maruyama T., 1988: Status of neutron monitors for radiation protection. Radioisotopes 37(11): 633-644