Cytoplasmic tyrosine kinase-linked receptors

Figure 4.20 Tyrosine kinase-linked receptors (a) those with inherentTK activity insulin receptor. The intracellular tail and cytoplasmic proteins become phosphoryLated following hormone engagement with the ligand-binding domain...

Ligand binding on the extracellular side is linked to stimulation of tyrosine kinase activity in the cytoplasmic receptor domain for receptors with intrinsic tyrosine kinase activity, the receptor tyrosine kinases (see 8.1). The hgand binding site and the tyrosine kinase are part of one and the same protein. 

An intensely investigated trophic factor is IGF-I, a pleiotropic protein important for normal development and maintenance of central and peripheral nervous system tissues. It interacts with the tyrosine kinase IGF-IR consisting of two extracellular a-subunits linked via disulfide bonds and two P-subunits, which are largely cytoplasmic and contain the tyrosine kinase domains. When activated by its substrate, IGF-I the IGF-IR signals to its major substrates, i.e., insulin receptor substrate-1 and -2 (IRS-1, IRS-2) and to She and from there on via the Ras/Raf pathway, via MEK and MAPK to the nucleus (Rubin and Baserga,... 

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