MADD, Blocking Peptide (MAP Kinase-activating Death Domain Protein, Differentially Expressed in Normal and Neoplastic Cells, DENN, Insulinoma Glucagonoma Clone 20, IG20, KIAA0358, Rab3 GDP/GTP Exchange Factor, RAB3GEP)

Peptide corresponding to amino acids 1570 to 1588 of human MADD (1). The sequence of immunogenic peptide is identical to that of DENN and differs by one amino acid with rat GDP/GTP exchange protein Rab3-GEP (2,5).\nMAP kinase-activating death domain protein (MADD) was initially identified as the type 1 tumor necrosis factor receptor (TNFR1) associated protein though their death domains (1). Overexpression of MADD activates MAP kinases ERK and JNK and induces the phosphorylation of cytosolic phospholipase A2 (1). MADD shares 98% identity with DENN (for differentially expressed in neoplastic vs. normal cells), which was recently identified as a substrate for c-jun N-terminal kinase 3 (JNK3) (2, 3). MADD has greater than 94% overall identity to a GDP/GTP exchange protein Rab3-GEP (4, 5). MADD is 87% identical to KIAA0358, a brain protein of unknown function (4). Identification of MADD as a component of the TNFR1 signaling complex and the similarity between MADD and Rab3-GEP provides a connection between TNFR1 activation and downstream MAP kinase activity through a guanine-nucleotide exchange protein.

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SPECIFICATIONS

Catalog Number

M1500P

Size

50ug

Form

Supplied as a lyophilized powder.

Purity

Purified 60-70%

References

1. Schievella AR, Chen JH, Graham JR, Lin LL. MADD, a novel death domain protein that interacts with the type 1 tumor necrosis factor receptor and activates mitogen-activated protein kinase. J Biol Chem 1997;272:12069-12075\n\n2. Chow VT, Lee SS. DENN, a novel human gene differentially expressed in normal and neoplastic cells. DNA Seq 1996;6:263-273 \n\n3. Zhang Y, Zhou L, Miller CA. A splicing variant of a death domain protein that is regulated by a mitogen-activated kinase is a substrate for c-Jun N-terminal kinase in the human central nervous system. Proc Natl Acad Sci U S A 1998;95:2586-2591\n\n4. Brown TL and Howe PH. MADD is highly homologous to a Rab3 guanine-nucleotide exchange protein (Rab3-GEP). Curr Biol 1998;8:R191\n\n5. Wada M, Nakanishi H, Satoh A, Hirano H, Obaishi H, Matsuura Y, Takai Y. Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins. J Biol Chem 1997;272:3875-3878.\n

Alternative Names

MAP-kinase Activating Death Domain