anti-Smad4 (human), Rabbit Monoclonal (RM277)

Members of the Smad family of signal transduction molecules are components of a critical intracellular pathway that transmits 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, 8; the common-mediator Smad (co-Smad), Smad4; and the antagonistic or inhibitory Smads (I-Smads), Smad6 and 7. Binding of the TGF-beta superfamily of ligands that includes Transforming Growth Factor-beta (TGF-beta) and bone morphogenetic protein (BMP) to its cognate receptor allows phosphorylation of Smad 1, 2, 3, 5 and 8 (R-Smad, Receptor Smad). This signals for heterotrimerization with Smad4 (co-Smad, co-mediator Smad) and translocation of the complex to the nucleus. Inhibitory or antagonistic Smad (I-Smad) that includes Smad 6 and 7, interact with activated R-Smads and attenuate the signaling pathway. Smad4 acts as a tumor suppressor protein by transcriptionally regulating its target genes such as Cyclin D1 (downregulation) and collagen (upregulation) that inhibit cell proliferation. Dephosphorylation regulates nuclear export and nucleocytoplasmic dynamics of Smads.