Protein tyrosine kinases cytoplasmic domain

The closely related Trk B serves as a receptor for BDNF. Two variants of this glycoprotein have been characterized a larger (145 kDa) form and a truncated (95 kDa) form. While exhibiting identical extracellular domains, the 95 kDa protein has a short (23 amino acid) cytoplasmic region, whereas the 145 kDa form displays a larger (tyrosine kinase) cytoplasmic domain. Trk B also serves as a functional receptor for NT-3 and NT-4/5 and is expressed widely throughout the central and peripheral nervous system. 

Receptor protein tyrosine kinases consist of an extracellular domain, a single transmembrane domain and a cytoplasmic domain 419... 

Insulin binding activates the tyrosine kinase activity associated with the cytoplasmic domain of its receptor as shown in F jure 1-9-4. There is no trimeric G protein, enzyme, or second messenger required to activate this protein tyrosine kinase activity ... 

Sadowski, I., Stone, J. C., and Pawson, T. (1986). A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag- s, Mol Cell Biol 6, 4396-408. 

The integrins do not have any enzyme activity in their own cytoplasmic domain, but on hgand binding, stimulation of tyrosine phosphorylation is observed on the cytoplasmic side of many cells, such as fibroblasts and platelets. The exact configuration of protein-protein interactions on the cytosolic side of the integrins is not clear and the mechanism of stimulation of protein tyrosine kinases is unknown. Some components of the focal adhesion points, such as the structural protein tensin, have SH2 and SH3 domains that may serve as specific attachment points for tyrosine kinases and other signal proteins. 

It is not known whether c-erbB-2 is a GFR since no ligand for it has yet been identified, but it may possess protein tyrosine kinase activity [21,22]. The sequence of the cytoplasmic domain encodes a tyrosine kinase-like domain very homologous to that of the EGF receptor. This homology (82%) is much higher than that seen between most of the members of the sre gene family (25-40%) and emphasizes the... 

Cytokine receptors are composed of two or more polypeptide chains. Some of these are shared between different receptors while others are unique to particular receptors. They all have (1) an N-terminal extracellular domain that provides binding sites for their cytokine ligands (2) a hydrophobic a-helix that spans the cell membrane and (3) a C-terminal cytoplasmic domain that contains binding sites for protein tyrosine kinases that play roles in signal transduction from these receptors (see Fig. 6-3). 

The cytoplasmic domains of cytokine receptors contain binding sites for protein tyrosine kinases called JAKs. Janus kinase). In the absence of a bound cytokine, the JAKs have low catalytic activity but they become highly active following cytokine binding. 

The cytoplasmic domains of all of these receptors have an intrinsic protein tyrosine kinase activity, and all the receptors have hydrophobic transmembrane sequences. Their extracellular regions are more variable in stmcture. Depending on the receptor, they may contain a range of domains, including (1) immrmoglobulin domains, (2) cysteine-rich motifs, (3) fibronectin type III repeats, and (4) EGF motifs. These can be present singly or in different combinations. Growth factor receptors are therefore examples of mosaic proteins. 

Typically, the activated protein tyrosine kinases of growth factor receptors catalyze the autophosphorylation of a number of tyrosine residues on the cytoplasmic domains of the adjacent receptor molecule. These phosphorylated residues provide docking sites for both effector and adaptor proteins that mediate downstream signaling pathways. 

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