Protein tyrosine kinases extracellular region

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 of receptor tyrosine kinases, binding of insulin to the extracellular domains of the IR causes autophosphorylation of specific tyrosine residues within the intracellular region of the [3 units. Some RTKs, as described above and as illustrated by JAKs described above and also shown in Figure 4.20, would at this point recruit adaptor proteins to bind directly to the phosphorylated intracellular... 

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. 

The neurotrophin receptor p75 was first identified as a nerve growth factor (NGF)-binding protein and was subsequently shown to interact with each of the other neurotrophic factors, BDNF, neurotrophin-3, and neurotrophin-4/-5. It also modulates the activity of several members of the tropomyosin-related receptor tyrosine kinase family (Trk) (reviewed in Chao, 2003). p75, a member of the tumor necrosis factor superfamily, is a type I transmembrane protein with four cysteine-rich domains in its extracellular region and a Death domain in its cytoplasmic protein (Fig. 11). 

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