Tyrosine cytoplasmic domain

FIGURE 4.2 Receptor tyrosine kinase dimerization. Binding of monomeric or dimeric ligands to RTK monomers leads to formation and stabilization of activated RTK dimers. Cytoplasmic domains of RTK are trans-phosphorylated by active FTK. 

In principle, RTK autophosphorylation could occur in cis (within a receptor monomer) or in trans (between two receptors in a dimer). In the first case, ligand binding would cause a change in receptor conformation that would facilitate c/ s-autophosphorylation of tyrosine residues located within or outside the PTK domain. In the second case, no conformational change must occur upon dimerization. The simple proximity effect would provide sufficient opportunity for trans-phosphorylation of tyrosines in the cytoplasmic domain by a second RTK. 

Figure 10.7 The EGF receptor. The N-terminal, extracellular region of the receptor contains 622 amino acids. It displays two cysteine-rich regions, between which the ligand-binding domain is located. A 23 amino acid hydrophobic domain spans the plasma membrane. The receptor cytoplasmic region contains some 542 amino acids. It displays a tyrosine kinase domain, which includes several tyrosine autophosphorylation sites, and an actin-binding domain that may facilitate interaction with the cell cytoskeleton...

The cytoplasmic domain of the P-subunit displays three distinct sub-domains (a) the juxtam-embrane domain , implicated in recognition/binding of intracellular substrate molecules (b) the tyrosine kinase domain, which (upon receptor activation) displays tyrosine kinase activity (c) the C-terminal domain, whose exact function is less clear, although site-directed mutagenesis studies implicate it promoting insulin s mitogenic effects. 

Bitopic proteins with a single transmembrane helix are more common. If oriented with the N-terminus extra-cytoplasmic, they are classified as type I or, if cytoplasmic, type II (Fig. 2-4). Bitopic membrane proteins are often involved in signal transduction, as exemplified by receptor-activated tyrosine kinases (Ch. 24) agonist occupation of an extracytoplasmic receptor domain can transmit structural changes via a single transmembrane helix to activate the latent kinase activity in a cytoplasmic domain. 

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 ... 

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... 

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