Home » , , » WNT signal transduction

WNT signal transduction

Course of the WNT signal transduction was less wing gene in Drosophila gene homologues first mammalian WNT genes are characterized by the INT-1 was found Roeland Nusse and Harold Varmus in 1982. The first pass WNT ligands have been shown to activate signal transduction processes that produce changes in gene expression, cell behavior, adhesion and polarity. In mammals, the WNT family of 19 proteins highly conserved molecules. WNT signaling has been described in at least three ways in which policies Canon is understood, the best procedure, WNT ligands bind to two different families of cell surface receptors, Frizzled (FZ) receptor and LDL receptor-related protein (LRP) family, and activate target genes through the balance of 尾 - catenin nuclear.

WNT proteins can also signal activation of calmodulin kinase II and protein kinase C (known as the WNT / Ca 2 +), an increase of intracellular Ca 2 +, or June kinase N-terminal (JNK) (known as the level of the polar cell processes) restructuring of the cytoskeleton that controls cell polarity WNT protein is secreted glycoproteins of 40 kDa, which held a number of cysteine ​​residues. Produced by different types of cells in humans, 19 WNT proteins have now been identified. It was found that the cysteine ​​palmitoylation is required for WNT proteins function, and told me to Porcupine (Porc), required for WNT-secreting cells, shows gay acyltransferases endoplasmic reticulum cancer (ER). Overall, it appears that Porc can the enzyme cis-and WNT signaling in stem cells and lung teine ​​palmitoylation is WNT proteins. In addition, studies in Drosophila revealed that seven trans membrane protein Wntless (WLS) and Event ness interrupted (IVE) is required for WNT secretion. Without WLS / Evi, primarily living in the Golgi devices, even Wnts WNT producing cells. In addition, extracellular sulfate proteoglycans HEPA (HSPGs) may also apply to transportation or balance WNT proteins.

Reception and WNT signal transduction related to interaction with WNT proteins are members of two different families of cell surface receptors, Frizzled (FZ) gene family and the LDL receptor-related protein family (LRP). FZ proteins bind Wnts through the extracellular N-terminal cysteine-rich domain (CRD), and most of WNT proteins can bind to several receptors, FZ, and vice versa .. Ten people FZ proteins have been identified so far, and the overall structure is similar to the seven trans membrane G protein-coupled receptors, suggesting that heterotrimeric G protein-FZ proteins can be used in WNT signal transduction. Molecule to one round of trans membrane family, prolactin inhibition, to identify LRP5 or 6, is also essential for signaling. It seems that the surface expression of both receptor families begin WNT signals, although the formation of complexes with trim eric molecules FZ WNT and LRP5 6 / has not been established. In addition, two tyrosine kinase receptors, hit and Ror2 been shown to bind to Wnts. Derailed binds Wnts through extracellular WIF (WNT inhibitory factor) domain, binds Wnts and the Ror2 CRD through WNT binding motif. At the end of the remarkable events of this alternative WNT receptors are largely unknown.

Protein excretion may be WNT ligands bind to receptors on the cell. The average pass Frizzled-related protein (SFRPs) and WNT inhibitory factor-1 (WIF-1). Human SFRP family consists of five members, each with CRD country. SFRPs biology, however, is complicated and in some cases WNT may act as agonists. WIF-1 has no sequence homology with SFRPs but contains one of the evolutionarily conserved WIF domain and five epidermal growth factor (EGF)-like repeats. The third type of extracellular inhibitor of WNT Dick Kopf represents (DKK) family, which antagonizes the WNT signaling pathway through inactivation of surface receptors LRP5 / 6

When WNT signaling is "off mode" 尾 cytosolic-catenin is phosphorylated on serine / threonine kinase casein kinase I (CKI) and GSK3 尾 at least four N-terminal residues. Scaffolding proteins ear and APC mediated interaction of kinase and 尾-catenin. These proteins form a complex 尾-catenin degradation, which makes 尾 phosphorylates-catenin recognize 尾 TrCP-directed ubiquitination and subsequent degradation and the proteasome. Nucleus, TCF protein / DNA binding forms a complex with Groucho and act as repressors are WNT target genes in WNT signal is absent.

Groucho can interact with histone deacetylase, which causes refraction of DNA transcription activation. The interaction with WNT ligands to receptors his FZ / LRP coreceptor complex activates the canonical signaling pathway. FZ can physically interact with Dishevelled (DVL), a cytosolic protein that acts as 尾-catenin and GSK3 kinase 尾. Furthermore, scaffolding protein translocates into the ear membrane, where it interacts with the intracellular tail of either inhibition of PRL or DVL FZ bound. Removing the complexity of the ear contributes to depletion 尾-catenin stability. "This" and "off" states in the WNT signaling DVL phosphorylation status control protein. It remains unclear however whether the WNT's commitment to FZ directly interact with the FZ-DVL DVL and phosphorylated active form of the WNT signal transduction. With the help of BCL9 尾 stable-catenin into the nucleus and competes with Groucho binding to TCF / LEF, recruits Pygopus and converts TCF suppression of WNT signaling in stem cells and lung Sør complex Activator complex backups. Several WNT signaling target genes, such as C-myC, Cyclanic D1, MMP-7 and WISPs have emerged.

WNT signaling path plays an important role in cell differentiation and proliferation, and various activities to promote the most characteristic of malignant tumors, including evasion of apoptosis, tissue invasion and metastasis, sustainable growth signals, insensitivity inhibitors and sustained growth angiogenesis.
Related Posts Plugin for WordPress, Blogger...

Free Mesothelioma Copyright © 2011 -- Template created by O Pregador -- Powered by Blogger