Receptor-like protein tyrosine

The receptor-like protein tyrosine phosphatases have a transmembrane and, in some cases, a large extracellular domain with a very variable structme (Fig. 8.16). Many, but not all, membrane protein tyrosine phosphatases have two catalytic domains in the cytoplasmic region. The complete structme is very similar to the structure of transmembrane receptors. Understanding of their function is far from complete. Both the natural ligands and the substrate proteins following in the sequence are incompletely characterized. Several studies have demonstrated a role for receptor-like PTPs in neuronal cell adhesion signaling pathways. In cells of the neural tissue, a surface protein, contactin has been identified as ligand for the extracellular domain of a protein tyrosine phosphatase (Peles et al., 1995). 

RPTPs = Receptor-like protein tyrosine phosphatases... 

Pot DA, Dixon JE (1992) Active site labeling of a receptor-like protein tyrosine phosphatase. J Biol Chem 267 140-143... 

Receptor-like protein tyrosine phosphatases Receptor tyrosine kinases Stress-activated PK/cJun N-terminal kinase SAPK/ERK kinase 1 Src homology domain 2 Transforming growth factor-(3 Tumour necrosis factor 12-O-tetradecanoylphorbol-13-acetate Tyrosine specific phosphatases... 

Hamanaka, H., N. Maeda, and M. Noda. 1997. Spatially and temporally regulated modification of the receptor-like protein tyrosine phosphatase /P isoforms with keratan sulphate in the developing chick brain. Eur. J. Neurosci 9 2297-2308. 

Streuli M, Krueger NX, Thai T et al (1990) Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR. EMBO J 9 2399-2407... 

In the continuing paper, Kreuter et al. reported the inhibition of intrinsic protein tyrosine kinase activity of the EGF-receptor kinase complex from human breast cancer cells by (-l-)-aeroplysinin-l (14) (273). Aeroplysinin-1, which possesses a close structure-relationship to tyrosine, blocks the epidermal growth factor (EGF) dependent proliferation of both MCF-7 and ZR-75-1 hmnan breast cancer cells, and inhibited the ligand-induced endocytosis of the EGF receptor in vitro. Aeroplysinin-1 was foimd to inhibit the tyrosine-specific phosphorylation of lipocortin-like proteins, which have been established as major substrates of the EGF receptor-associated protein-tyrosine kinase... 

Like all immunoreceptor family members, FceRI lacks intrinsic tyrosine kinase activity. IgE and antigen-induced crosshnking of FceRI initiates a complex series of phosphate transfer events via the activation of non-receptor Src, Syk and Tec family protein tyrosine kinases (fig. 1). The Src family kinase Lyn, which associates with the FceRI p subunit in mast cells, transphosphorylates neighboring FceRI ITAMs after receptor aggregation [7, 26]. Once phosphorylated, the p chain ITAM binds to the SH2 domain of additional Lyn molecules, while the phosphorylated y chain ITAM recruits Syk to the receptor complex, where it is activated by both autophosphorylation and phosphorylation by Lyn [2, 7,15, 26]. 

Activation of PI-PLC-linked receptors, such as the mAChR, results in increased PKC activity. Since the addition of phorbol esters, which are PKC agonists (see Ch. 20), results in phosphorylation of Raf, this mechanism may provide an explanation for the ability of PI-PLC-coupled receptors to activate MAPK. A recently discovered protein tyrosine kinase PYK2, which is enriched in the CNS, is also activated by PKC. Like PTK-X, PYK2 phosphorylates SHC and recruits the Grb2-SOS complex, which results in activation of the MAPK cascade. PYK2 is also activated by... 

FIGURE 1 2-2 Schematic diagram of the phosphorylation sites on each of the four 60kDa subunits of tyrosine hydroxylase (TOHase). Serine residues at the N-terminus of each of the four subunits of TOHase can be phosphorylated by at least five protein kinases. (J), Calcium/calmodulin-dependent protein kinase II (CaM KII) phosphorylates serine residue 19 and to a lesser extent serine 40. (2), cAMP-dependent protein kinase (PKA) phosphorylates serine residue 40. (3), Calcium/phosphatidylserine-activated protein kinase (PKC) phosphorylates serine 40. (4), Extracellular receptor-activated protein kinase (ERK) phosphorylates serine 31. (5), A cdc-like protein kinase phosphorylates serine 8. Phosphorylation on either serine 19 or 40 increases the activity of TOHase. Serine 19 phosphorylation requires the presence of an activator protein , also known as 14-3-3 protein, for the expression of increased activity. Phosphorylation of serines 8 and 31 has little effect on catalytic activity. The model shown includes the activation of ERK by an ERK kinase. The ERK kinase is activated by phosphorylation by PKC. (With permission from reference [72].)... 

FIGURE 24-10 Schematic structures of nonreceptor protein tyrosine phosphatases (NRPTPs) and receptor protein tyrosine phosphatases (RPTPs). NRPTPs contain a catalytic domain and various regulatory domains. RPTPs are composed of an extracellular domain, a transmembrane domain and an intracellular domain with one or two catalytic domains. Like receptor protein tyrosine kinases, the structural features of the extracellular domains divide the RPTPs into different families. (With permission from reference [12]). 

---