癌症中SMAD2/3磷酸化基序突变
中文名称
通路描述
SMAD2和SMAD3的C末端保守磷酸化基序Ser-Ser-X-Ser在癌症中易发生破坏性突变。该基序中的最后两个丝氨酸残基，即SMAD2中的Ser465和Ser467，以及SMAD3中的Ser423和Ser425，由活化的TGFβ受体复合物磷酸化。一旦磷酸化，SMAD2和SMAD3将与SMAD4形成具有转录活性的异三聚体。由于丝氨酸残基被不能磷酸化的氨基酸残基取代，或者磷酸化基序从蛋白质序列中缺失或截短，SMAD2和SMAD3的磷酸化基序突变体也无法被TGFβ受体复合物激活。
英文描述
SMAD2/3 Phosphorylation Motif Mutants in Cancer The conserved phosphorylation motif Ser-Ser-X-Ser at the C-terminus of SMAD2 and SMAD3 is subject to disruptive mutations in cancer. The last two serine residues in this conserved motif, namely Ser465 and Ser467 in SMAD2 and Ser423 and Ser425 in SMAD3, are phosphorylated by the activated TGF beta receptor complex (Macias Silva et al. 1996, Nakao et al. 1997). Once phosphorylated, SMAD2 and SMAD3 form transcriptionally active heterotrimers with SMAD4 (Chacko et al. 2001, Chacko et al. 2004). Phosphorylation motif mutants of SMAD2 and SMAD3 cannot be activated by the TGF-beta receptor complex either because serine residues are substituted with amino acid residues that cannot be phosphorylated or because the phosphorylation motif is deleted from the protein sequence or truncated (Fleming et al. 2013).
所含基因
3 个基因