Phospho-SMAD2 (Ser465/467) (138D4) Rabbit mAb

Members of the SMAD family of signal transduction molecules are components of a critical intracellular pathway that transmit TGF-β signals from the cell surface into the nucleus. Three distinct classes of SMADs have been defined: the receptor-regulated SMADs (R-SMADs), which include SMAD1, 2, 3, 5, and 9; the common-mediator SMAD (co-SMAD), SMAD4; and the antagonistic or inhibitory SMADs (I-SMADs), SMAD6 and 7 (1-5). Activated type I receptors associate with specific R-SMADs and phosphorylate them on a conserved carboxy-terminal SSXS motif. The phosphorylated R-SMADs dissociate from the receptor and form a heteromeric complex with SMAD4, initiating translocation of the heteromeric SMAD complex to the nucleus. Once in the nucleus, SMADs recruit a variety of DNA binding proteins that function to regulate transcriptional activity (6-8).Following stimulation by TGF-β, Smad2 and Smad3 become phosphorylated at their carboxy-termini (Ser465/467 on Smad2; Ser423/425 on Smad3) by the receptor kinase TGF-β R1 (9-11). Following phosphorylation, Smad2 and Smad3 form a heteromeric complex with the co-Smad family member Smad4. These complexes are translocated to the nucleus where they bind DNA and regulate gene transcription. 1.Heldin, C.H. et al. (1997) Nature 390, 465-71. 2.Attisano, L. and Wrana, J.L. (1998) Curr Opin Cell Biol 10, 188-94. 3.Derynck, R. et al. (1998) Cell 95, 737-40. 4.Massagué, J. (1998) Annu Rev Biochem 67, 753-91. 5.Whitman, M. (1998) Genes Dev 12, 2445-62. 6.Wrana, J.L. (2000) Sci STKE 2000, re1. 7.Attisano, L. and Wrana, J.L. (2002) Science 296, 1646-7. 8.Moustakas, A. et al. (2001) J Cell Sci 114, 4359-69. 9.Abdollah, S. et al. (1997) J Biol Chem 272, 27678-85. 10.Souchelnytskyi, S. et al. (1997) J Biol Chem 272, 28107-15. 11.Liu, X. et al. (1997) Proc Natl Acad Sci U S A 94, 10669-74.