Receptor tyrosine kinases recognition

Transmembrane receptors include G-protein-coupled receptors, receptor tyrosine kinases, integrins, pattern-recognition receptors and hgand-activated ion channels. 

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. 

The insulin receptor is composed of two heterodimers each heterodimer is composed of an a unit and a P unit. The a unit is extracellular and contains the insulin recognition and binding sites the p unit spans the cellular membrane and contains a tyrosine kinase. Although insulin can bind to a single ap dimer, it binds with higher affinity to the aPaP tetrameric complex. When insulin binds to an a unit, the tyrosine kinase associated with the corresponding p unit is stimulated. Following this, intracellular proteins such as IRS-1 and IRS-2 (IRS=insulin receptor substrate) are phosphorylated by the P subunit tyrosine kinase, and they in turn activate a network of phosphorylations within the receptor cell. 

Cytokines all function using a group of transmembrane receptors embedded in the plasma membranes of target cells. The receptors have no tyrosine kinase activity but associate with and activate kinases known as Janus kinases (JAKs). These kinases phosphory-late tyrosine side chains in their receptors, and the phosphorylated receptors activate transcription factors of the STAT (signal transducer-activators of transcription) group.186-195 The specificity of cytokine action results from a combination of receptor recognition and recognition of the various STAT molecules by different JAKs.111 Cytokines have a variety of structures. Many are helix bundles or have (3 sheet structures (Fig. 30-6). 

Phosphotyrosine phosphatases are integrated just like tyrosine Idnases into signalling pathways. They interact with receptors and have recognition motifs that direct diem to their targets. 5 Protein phosphotyrosine phosphatases downregulate tyrosine phosphorylation and play a role in cellular regulation as important as that of protein tyrosine kinases. 

B. S. Gaul, M.L. Harrison, R.L. Geahlen, R.A. Burton, and C.B. Post. 2000. Substrate recognition by the Lyn protein-tyrosine kinase NMR structure of the immunoreceptor tyrosine-based activation motif signaling region of the B cell antigen receptor Biol. Chem. 275 16174-16182. (PubMed)... 

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