MET receptor tyrosine kinase

Rodrigues GR, Park M. 1993. Dimerization through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase. Mol Cell Biol 13 6711-6722. 

Weidner, K. M., Sachs, M. and Birchmeier, W. (1993a) The met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of HGF/SF in epithelial cells. J. Cell Biol. 121, 145-154. 

Recently, Campbell et al. (2009) have reported that disrupted MET gene signaling may contribute to increased risk for autism spectrum disorder that includes familial GI dysfunction. A functional variant in the promoter of the gene encoding the MET receptor tyrosine kinase has been associated with ASD, and MET protein expression has been found to be decreased in the temporal lobe cortex in ASD postmortem brain tissue. MET is a pleiotropic receptor that is known to function in both brain development and GI repair. Thus, the identification of medical disorders in ASD individuals, in this case GI disorders, may not only improve quality of life for those affected with ASD but may lead to improved or more precise definition of genetic and phenotypic subtypes in this complex heterogeneous disorder. 

Westerhoff M, Faoro L, Loganathan S, et al. Immrmohisto-chemical (IHC) expression of c-Met receptor tyrosine kinase (c-Met) has prognostic significance and its activation is related to phosphorylated protein kinase Cff (p-PKC ff) in malignant mesothelioma (MM). Mod Pathol. 2008 21 353A. 

Weidner, K.M. et al.. Interaction between Gabl and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis, 7/oi re, 384,173,1996. 

Maroun, C.R. et al.. The Gabl PH domain is required for localization of Gabl at sites of cellcell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase. Mol. Cell. Biol, 19,1784, 1999. 

Diaryl-substituted pyrrolo[3,2-6]pyridine-5-carbonitriles 63 exhibiting c-Met receptor tyrosine kinase inhibition activity were reported. The key intermediates 64 were prepared using the Larock indole synthesis. A variety of aryl/heteroaryl substitution in the 2-position was then efficiently explored from the corresponding iodo analogs 65. 

The c Met receptor tyrosine kinase is one of the RTKs most frequently mutated or abnormally activated in late stage human cancers, and plays a critical role in regulation of tumor progression, invasive growth, and tumor angiogenesis. The triazolopyrazine core was discovered to yield potent... 

Han, C., Michalopoulos, G., and Wu, T. (2006). Prostaglandin E2 receptor EPl transactivates EGFR/Met receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells. J. Cell Physiol. 207, 261-270. 

The Sema domain consisting of about 500 amino acids is characterized by highly conserved cysteine residues that form intramolecular disulfide bonds. Crystal structures have revealed that the Sema domain folds in the manner of the (3 propeller topology which is also found in integrins or the low-density lipoprotein (LDL) receptors. Sema domains are found in semaphorins, plexins and in the receptor tyrosine kinases Met and Ron. 

Figure 14.21 The modular structure of Insulin receptor substrates IRS-1 and IRS-2 This schematic view represents the amino acid sequence common to IRS-1 and lRS-2. Each protein contains a pleckstrin homology domain (which binds phosphoinositide lipids), a phospbotyrosine-binding domain, and four sequences that approximate Tyr-X-X-Met (YXXM). The latter are phosphorylated by the insulin receptor tyrosine kinase.

Four sequences that approximate the form Tyr-X-X-Met are present in each IRS protein. Such sequences are the preferred targets for the receptor tyrosine kinase. Thus, the activated insulin receptor kinase phosphorylates these tyrosine residues. In their phosphorylated form, the IRS molecules act as adaptor proteins they do not activate the next component of the pathway, a lipid kinase rather, they bind to the lipid kinase and bring it to the membrane so that it can act on its substrate, a membrane lipid. 

Met/hepatocyte growth factor receptor tyrosine kinase <45> [121]... 

Ferracini, R. Longati, R Naldini, L. Vigna, E. Comoglio, P.M. Identification of the major autophosphorylation site of the Met/hepatocyte growth factor receptor tyrosine kinase. J. Biol. Chem., 266, 19558-19564 (1991)... 

Paul, S.R. Merberg, D. Finnerty, H. Morris, G.E. Morris, J.C. Jones, S.S. Kriz, R. Turner, K.J. Wood, C.R. Molecular cloning of the cDNA encoding a receptor tyrosine kinase-related molecule with a catalytic region homologous to c-met. Int. J. Cell Cloning, 10, 309-314 (1992)... 

RTKs represent pivotal targets in approaches toward cancer therapy. Thns, c-Met, c-Kit, as well as EGFR are important receptor tyrosine kinases that have been implicated in the etiology of multiple tumor types, and they are important therapeutic targets. 

These results confirmed the notion that the PAH component can have a direct negative impact on the developmental expression of (i) key glutamatergic regulators of NMDA-mediated processes (receptor tyrosine kinase-MET) and (ii) behavioral deficit phenotypes. 

Sheng, L., Ding, X., Ferguson, M., et al., 2010. Prenatal polycyclic aromatic hydrocarbon exposure leads to behavioral deficits and downregulation of receptor tyrosine kinase, MET. Toxicol. Sci. 118, 625-634. 

Jeffers, M., G. A. Taylor, K. M. Weidner, S. Omura, and G. F. Vande Woude. Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway. Mol Cell Biol. 17 799-808.1997. 

Jakob CA, Burda P, Roth J, Aebi M (1998) Degradation of misfolded endoplasmic reticulum glycoproteins in Saccharomyces cerevisiae is determined by a specific oligosaccharide structure. J Cell Biol 142 1223-1233 Janson LW, Ragsdale K, Luby-Phelps K (1996) Mechanism and size cutoff for steric exclusion from actin-rich cytoplasmic domains. Biophys ) 71 1228-1234 Jeffers M, Taylor GA, Weidner KM, Omura S, Vande Woude GF (1997) Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway. Mol Cell Biol 17 799-808... 

---