PHARMACOLOGY

 transduction mechanism of kinase linked receptors

The first step following agonist bluiding is dimerisation which leads to autophosphorylation of the intracellular domain of each receptor SH2-domian proteins then bind to the phosphorylated receptor and are themselves phosphorylated Two well-characterised pathways are shown: [A] The growth factor (Ras/Raf) pathway : [B] The cytokine (jak stat) pathway 

    Molecular structure of Type III receptors comprises at very large extracellular (ligand-binding) and intracellular (catalytic effector) domains of 400-700 residues (in insulin receptors ) or 1000 residues (receptors for growth factors ) There is a single a-helix in transmembrane region In all cases these receptors trigger a kinase cascade This Signal transduction mechanism involves dimerisation of receptors followed by autophosphorylation of tyrosine residue This phosphorylated tyrosine residue then acts as acceptor for the SH2 domains of a variety at intracellular proteins which in turn control various cell functions These receptors are mainly involved in controlling cell growth and differentiation and act indirectly by regulating gene transcription There are two main pathways of signal transduction mechanisms after tyrosine residue has been phosphorylated One is for growth factor which involve Ras/Raf/MAP kinase pathway and it is important in cell division growth and differentiation The other is activated by various cytokines and involves Jak/Stat This is important to control the synthesis and release of many inflammatory mediators