Tyrosine-related proteins

Another milestone in this research area was the isolation and identification of antigens from tumor tissue [e.g., tyrosine-related proteins (TRP)-1 and (TRP)-2]. After the administration of these antigens, it became clear that a sufficient success was only possible by the concomitant administration of adjuvant-acting substances like CpG-oligonucleotides (8). 

Construction of a Liposomal Carrier for Tyrosine-Related Protein-2 Peptide at Lab Scale... 

Activation of Dendritic Cells by Liposomes Containing Tyrosine-Related Protein-2 Peptides... 

Melanin biosynthesis in animals is a complex process starting with the L-tyrosine amino acid. In the first step, L-tyrosine is converted first into DOPA and then into dopaquinone, a process catalyzed by tyrosinase. In the biosynthesis of eumelanins, dopaquinone undergoes a cyclization to form dopachrome and subsequently a tau-tomerization into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). DHICA is further oxidized to indole-5,6-quinone2-carboxylic acid, the precnrsor of DHICA eumelanins. Tyrosinase-related proteins TRP-2 and TRP-1, respectively, are responsible for the last two steps, and they are under the control of the tyrosinase promoter. 

MAPK kinase (MAPKK). MAPK kinase itself is activated by phosphorylation by still another protein kinase, termed MAPK kinase kinase (MAPKKK). MAPK kinase kinase is activated upon interaction with a member of the Ras superfamily of small G proteins, which are bound to the plasma membrane (see Ch. 19). The exact mechanism of activation remains unknown, but it is believed that Ras and related proteins, in the activated GTP-bound form, can bind MAPK kinase kinase and thereby draw the kinase to the plasmalemma, where it is activated by as yet unknown factors, perhaps even an additional kinase, MAPK kinase kinase kinase (MAPKKKK). The mechanism governing the activation of Ras and related proteins by extracellular signals is quite complex and involves numerous Tinker proteins, for example She, Grb and Sos, that couple Ras to a variety of plasmalemma-associated growth factor-protein tyrosine kinase receptors (see Chs 20,24 and 27). 

Figure 2.20 Schematic representation of a zinc-finger domain from TFIIIA and related proteins. X represents any amino acid conserved amino acids are histidine (H), cysteine (C), tyrosine (Y), phenylalanine (F), and leucine (L).

Fibroblast growth factor, FGF-1, FGF-2, FGF-3, FGF-4. related proteins of 16-32 kD Receptor tyrosine kinase... 

Burkhardt, A. L., Bmnswick, M., Bolen, J. B., and Mond, J. J. (1991). Anti-immunoglobulin Stimulation of B Lymphocytes Activates src-Related Protein-Tyrosine Kinases. Proc Natl Acad Sci USA 88 7410. 

EPH A subfamily of RTK s, receptor tyrosine kinases. Related proteins are ELK, EPH-Ijke Kinase, ERK, ELK-Related Kinase, and ECK. epithelial Cell Kinase. Overexpresion of EPH causes cancer. 

The study by Martin et al. is of interest not only for the rationalization of the electrometric and spectrophotometric measurements in terms of the microconstants, but also because the spectrophotometric titration of tyrosine relates so closely to similar studies in proteins. In particular, the multiple H+-equilibria of tjnrosine result from the close juxtaposition of amino and phenolic groups in the same molecule under these circumstances the ionizations are mutually interacting. We suggest that some of the anomahes seen in t3Tosyl ionization in proteins may arise in a similar fashion, but in terms of magnitude, this mechanism clearly cannot account for such anomalous tjn-osyl groups as those seen in ribonuclease or ovalbumin. 

A phosphotyrosine residue in the carboxyl terminus of Src and related protein tyrosine kinases binds to its own SH2 domain to generate the inhibited from of Src (Section 15.5). Removal of the phosphate from this residue will activate the kinase. 

Cui L, Yu WP, DeAizpurua HJ et al (1996) Cloning and characterization of islet cell antigen-related protein-tyrosine phosphatase (PTP), a novel receptor-Hke PTP and autoantigen in insulin-dependent diabetes. J Biol Chem 271 24817-24823... 

Inhibition of EGF-R tyrosine kinase by hypericin 1 was shown to be irreversible, non-competitive and time as well as temperature dependent. The IC50 increased from 0.75 pM in the dark to 44 nM with light illumination for 30 min. This effect was presumably due to a type I photosensitization mechanism since exclusion of oxygen did not alter the inhibition curve. Some Ser/Thr protein kinases (e.g., protein kinase A, casein kinase 1 and 2) and the enzyme 5 -nucleotidase were not inhibited even at concentrations > 100 pM [144]. However, the same authors recently reported that hypericin 1 in addition to protein kinase C also caused the light-dependent inhibition of certain other Ser/Thr kinases (e.g. protein kinase CK-2, mitogen-activated kinase) and the insulin receptor tyrosine kinase, while it was ineffective towards the cytosolic tyrosine kinases Lyn, Fgr, TPK-IIB and CSK. These results suggest that distantly related protein kinases could still share common reactive domains for the interaction with hypericin 1 [156]. In contrast to the above mentioned studies, Richter and Davies [157] observed no inhibition of EGF-induced tyrosine phosphorylation of the EGF-R in HN5 squamous carcinoma... 

These receptors are a family of closely related proteins (see Figure 23.15), sharing amino acid sequence homology in the domains with tyrosine kinase activity. There is evidence that the action of insulin as a growth factor is mediated through its binding to one of these receptors, the IGF-1 receptor. 

ATP + protein tyrosine = ADP + protein tyrosine phosphate (<1> regulation of mitosis, differentiation, migration, neovascularization, and apoptosis [40] <1> PTKs are closely related with cell groth, proliferation, differentiation and signalling of the immune system)... 

Superi-Furga, G. Courtneidge, S.A. Structure-function relationships in Src family and related protein tyrosine kinases. BioEssays, 17, 321-330 (1995)... 

Eph-related receptor tyrosine kinase Cek9 <220> [545] epidermal growth factor receptor-related protein epithelial and endothelial tyrosine kinase epithelial cell kinase ErbB-4 receptor <230> [566]... 

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