IndraLab

"BMP receptors activate Smad1, Smad5, and Smad8 (called BR-Smads in this review) whereas Smad2 and Smad3 are phosphorylated by the activin of Tgfbeta recepetors ALK3 and ALK6 can activate all three BR-Smads but ALK2 only phophorylates SMAD1 and SMAD5"

"c-Jun NH(2)-terminal kinase tended to induce the phosphorylation of Smad2/3L in human colorectal adenoma-carcinoma sequence (phosphorylation increases formation of SMAD234 complex)"

"GnRH in a dose--(0.01 to 10 microM) and time--(5 to 30 min) dependent manner decreased the rate of Smad3 activation (phospho-Smad3, pSmad3), and altered Smad3 cellular distribution in both cell types."

"TGF-B1 is the most abundant and universally expressed isoform; most studies have either examined or been performed with exogenous TGF-B1. TGF-B is secreted into the extracellular matrix as a latent protein complex bound to a latency- associated protein and one of the four isoforms of latent TGF-B binding protein. Activation of TGF-B, which is required for biologic activity, occurs through poorly understood mechanisms likely involving proteolytic processing of the associated proteins and release of the TGF-B ligand. Once activated, the TGF-B ligands regulate cellular processes by binding to three high-affinity cell surface receptors: the type I TGF-B receptor (TBRI), type II TGF-B receptor (TBRII), and type III TGF-B receptor (TBRIII, also referred to as betaglycan). Where expressed, TBRIII is the most abundant TGF-B receptor and classically functions by binding the TGF-B ligand and transferring it to its signaling receptors, TBRI and TBRII.12 TBRI and TBRII contain serine/threonine protein kinases in their intracellular domains. TBRI initiates intracellular signaling by phosphorylating a family of transcription factors, the Smads. Smad2 and Smad3 are the receptor-activated Smads for TGF-B because they are phosphorylated by TBRI. Smad4 is a common partner for all of the receptor-activated Smads. Smad6 and Smad7 are inhibitory Smads that block the phosphorylation of Smad2 or Smad3, thus inhibiting TGF-B signaling. A general mechanism for TGF-B signaling has been elucidated (Fig 1).13,14 The TGF-B ligand either binds to TBRIII, which presents TGF-B to TBRII, or binds to TBRII directly. Once bound to TGF-B, TBRII recruits, binds, and transphosphorylates TBRI, thereby stimulating its protein kinase activity. The activated TBRI phosphorylates Smad2 or Smad3, which binds to Smad4. The resulting Smad complex translocates into the nucleus and interacts in a cell specific manner with transcription factors to regulate specifically the transcription of a multitude of TGF-B responsive genes"

"BMP receptors activate Smad1, Smad5, and Smad8 (called BR-Smads in this review) whereas Smad2 and Smad3 are phosphorylated by the activin of Tgfbeta recepetors ALK3 and ALK6 can activate all three BR-Smads but ALK2 only phophorylates SMAD1 and SMAD5"

"TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, was also suppressed by VEGF. VEGF attenuation of TGF-beta action was also demonstrated in two other endothelial cell lines. In conclusion, VEGF attenuates TGF-beta action in the human endothelial cell, specifically at the level of transcription of PAI-1 gene and Smad2/3 phosphorylation"

"TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, was also suppressed by VEGF. VEGF attenuation of TGF-beta action was also demonstrated in two other endothelial cell lines. In conclusion, VEGF attenuates TGF-beta action in the human endothelial cell, specifically at the level of transcription of PAI-1 gene and Smad2/3 phosphorylation"

"TGF-B1 is the most abundant and universally expressed isoform; most studies have either examined or been performed with exogenous TGF-B1. TGF-B is secreted into the extracellular matrix as a latent protein complex bound to a latency- associated protein and one of the four isoforms of latent TGF-B binding protein. Activation of TGF-B, which is required for biologic activity, occurs through poorly understood mechanisms likely involving proteolytic processing of the associated proteins and release of the TGF-B ligand. Once activated, the TGF-B ligands regulate cellular processes by binding to three high-affinity cell surface receptors: the type I TGF-B receptor (TBRI), type II TGF-B receptor (TBRII), and type III TGF-B receptor (TBRIII, also referred to as betaglycan). Where expressed, TBRIII is the most abundant TGF-B receptor and classically functions by binding the TGF-B ligand and transferring it to its signaling receptors, TBRI and TBRII.12 TBRI and TBRII contain serine/threonine protein kinases in their intracellular domains. TBRI initiates intracellular signaling by phosphorylating a family of transcription factors, the Smads. Smad2 and Smad3 are the receptor-activated Smads for TGF-B because they are phosphorylated by TBRI. Smad4 is a common partner for all of the receptor-activated Smads. Smad6 and Smad7 are inhibitory Smads that block the phosphorylation of Smad2 or Smad3, thus inhibiting TGF-B signaling. A general mechanism for TGF-B signaling has been elucidated (Fig 1).13,14 The TGF-B ligand either binds to TBRIII, which presents TGF-B to TBRII, or binds to TBRII directly. Once bound to TGF-B, TBRII recruits, binds, and transphosphorylates TBRI, thereby stimulating its protein kinase activity. The activated TBRI phosphorylates Smad2 or Smad3, which binds to Smad4. The resulting Smad complex translocates into the nucleus and interacts in a cell specific manner with transcription factors to regulate specifically the transcription of a multitude of TGF-B responsive genes"

"c-Jun NH(2)-terminal kinase tended to induce the phosphorylation of Smad2/3L in human colorectal adenoma-carcinoma sequence (phosphorylation increases formation of SMAD234 complex)"

"Ras acting via Erk MAP kinases causes phosphorylation of Smad2 and Smad3 at specific sites in the region linking the DNA-binding domain and the transcriptional activation domain."

"Ras acting via Erk MAP kinases causes phosphorylation of Smad2 and Smad3 at specific sites in the region linking the DNA-binding domain and the transcriptional activation domain."

"GnRH in a dose--(0.01 to 10 microM) and time--(5 to 30 min) dependent manner decreased the rate of Smad3 activation (phospho-Smad3, pSmad3), and altered Smad3 cellular distribution in both cell types."