Negative regulation of TGFβ signaling by the kinase LKB1 and the scaffolding protein LIP1.

摘要: Signal transduction by the Smad pathway elicits critical biological responses to many extracellular polypeptide factors, including TGFβ and bone morphogenetic protein. Regulation of signaling imparts several cytoplasmic nuclear mechanisms, some which entail protein phosphorylation. Previous work established a complex between Smad4 scaffolding LKB1-interacting 1 (LIP1). LKB1 is well studied tumor suppressor kinase that regulates cell growth polarity. Here, we analyzed LKB1-LIP1 Smad4-LIP1 complexes found LIP1 can self-oligomerize. We further demonstrate capable phosphorylating on Thr77 its DNA-binding domain. inhibits from binding either TGFβ- or protein-specific promoter sequences, correlates with negative regulatory effect exerts Smad4-dependent transcription. Accordingly, negatively gene epithelial-mesenchymal transition. Thus, provide control signaling.