TGF-beta / Smad signaling pathway inhibitor (TGF-beta / Smad)
Nine species SMAD have been found in protein family, called SMAD1-9,which were all found involved in TGF-BETA signal transduction. They are its receptor downstream signaling molecules, including receptor type, common media type, suppression type.
The main steps of the signal transduction of TGF-BETA family are:
1, TGF-BETA factors (the ligand) react with receptors with serine / threonine kinase activity (Tbeta receptors I and II) on the corresponding film; then the ligands activate receptor II by phosphorylation, followed by the formation of a complex after the phosphorylation i.e. activation of receptor I by the former activated receptor II.
2, the signal transduction of TGF-BETA family within the cytoplasm:
After activated, the receptors react with SMAD intermediary protein to form heterologous oligomers, which will convey the signals of TGF-BETA family to the nucleus.
3, the signal transduction of TGF-BETA family within the nucleus:
Nuclear SMAD oligomer as a transcription factor directly reacts with DNA, or in combination with other transcription factors and activated factors, to induce the transcription response of TGF-BETA signal, in order to adjust the transcription of corresponding target genes.
SMAD family are a class of single polypeptide chains with a molecular weight of 40-60KD. There are three basic functional areas on the single polypeptide chain: conserved amino-terminal region MH1 and carboxy-terminal region MH2 and the polytropic linkage region in the middle. The linkage region is the proline-rich hinge region comprising a plurality of phosphorylation sites, including MAP kinase phosphorylation sites. After phosphorylated by ERK, MAP kinase phosphorylation sites can inhibit nuclear transfer of SMAD proteins, which makes themselves the negative regulatory region of SMAD. TGF0-BETA itself is the stimulus of SMAD and SMAD1, 2, 3, 4 can be activated by it.
In addition, SARA (an anchoring protein) plays a role as a bridge between SMAD2, 3 and TGF-BETA receptors, and it can also participate in and promote its binding between them.