PMID- 10640736 OWN - NLM STAT- MEDLINE DCOM- 20000224 LR - 20190515 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 164 IP - 3 DP - 2000 Feb 1 TI - Phosphorylation of FADD/ MORT1 at serine 194 and association with a 70-kDa cell cycle-regulated protein kinase. PG - 1236-42 AB - The adapter molecule Fas-associated death domain protein (FADD)/mediator of receptor-induced toxicity-1 (MORT1) is essential for signal transduction of the apoptosis-inducing receptor CD95 (APO-1/Fas) as it connects the activated receptor with the effector caspase-8. FADD also plays a role in embryonic development and the cell cycle reentry of T cells. FADD is phosphorylated at serine residues. We now show that phosphorylation exclusively occurs at serine 194. The phosphorylation of FADD was found to correlate with the cell cycle. In cells arrested at the G2/M boundary with nocodazole, FADD was quantitatively phosphorylated, whereas only nonphosphorylated FADD was found in cells arrested in G1/S with hydroxyurea. In this context, we have identified a 70-kDa cell cycle-regulated kinase that specifically binds to the C-terminal half of FADD. Because CD95-mediated apoptosis is independent of the cell cycle, phosphorylation of FADD may regulate its apoptosis-independent functions. FAU - Scaffidi, C AU - Scaffidi C AD - Tumor Immunology Program, Applied Tumorvirology, German Cancer Research Center, Heidelberg, Germany. FAU - Volkland, J AU - Volkland J FAU - Blomberg, I AU - Blomberg I FAU - Hoffmann, I AU - Hoffmann I FAU - Krammer, P H AU - Krammer PH FAU - Peter, M E AU - Peter ME LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (FADD protein, human) RN - 0 (Fas-Associated Death Domain Protein) RN - 0 (Recombinant Fusion Proteins) RN - 0 (fas Receptor) RN - 452VLY9402 (Serine) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) SB - AIM SB - IM MH - *Adaptor Proteins, Signal Transducing MH - Burkitt Lymphoma MH - Carrier Proteins/genetics/*metabolism MH - Cell Cycle/immunology MH - Cell Line MH - Cyclin-Dependent Kinases/*metabolism MH - Cytotoxicity, Immunologic/genetics MH - Fas-Associated Death Domain Protein MH - Genetic Vectors/chemical synthesis/metabolism MH - Humans MH - Molecular Weight MH - Phosphorylation MH - Recombinant Fusion Proteins/metabolism MH - Serine/*metabolism MH - Transfection MH - Tumor Cells, Cultured MH - fas Receptor/genetics/*metabolism EDAT- 2000/01/21 09:00 MHDA- 2000/02/26 09:00 CRDT- 2000/01/21 09:00 PHST- 2000/01/21 09:00 [pubmed] PHST- 2000/02/26 09:00 [medline] PHST- 2000/01/21 09:00 [entrez] AID - ji_v164n3p1236 [pii] AID - 10.4049/jimmunol.164.3.1236 [doi] PST - ppublish SO - J Immunol. 2000 Feb 1;164(3):1236-42. doi: 10.4049/jimmunol.164.3.1236.