Signal transduction receptor tyrosine kinases

Waters, C., Pyne, S., et al. (2004). The role of G-protein coupled receptors and associated proteins in receptor tyrosine kinase signal transduction. Semin Cell Dev Biol 15(3) 309-23. 

Phosphohpases of type Cy are activated by receptor tyrosine kinases (see Chapter 8), and thus phosphohpase Cy is involved in growth factor controlled signal transduction pathways. The receptor tyrosine kinases (see Chapter 8) phosphorylate the enzyme at specific tyrosine residues and initiate activation of the enzyme. Characteristic for the structure of phospholipase Cy is the occurrence of SH2 and SH3 domains (see Chapter 8). These represent protein modules that serve to attach further partner proteins. 

Autophosphorylation and phosphorylation of substrate proteins are essential elements of signal transduction via receptor tyrosine kinases. Autophosphorylation fre-... 

Fig. 8.6. Functions of autophosphorylation of receptor tyrosine kinases. Autophosphorylation of receptor tyrosine kinases takes place in trans, i.e., between neighboring protomers of the receptor. The catalytic domain of the receptor is shown as a shaded segment. As a consequence of autophosphorylation, the intrinsic tyrosine kinase activity of the receptor is stimulated. Effector proteins can also bind to the activated receptor. Binding takes place with specific phosphotyrosine binding domains (SH2 or PTB domains) at phosphotyrosine residues of the activated receptor. A critical factor for further signal transduction is the membrane association of the effector proteins that enter into binding with the activated receptor. Details of the effector proteins can be found as follows phospholipase Cy 5.6.2 Src kinase 8.3.2 pl20 GAP 9.4 Grb2, She, IRS 8.5 PI3-kinase 6.6.1 Syp tyrosine phosphatase 8.4.

Autophosphorylation of receptor tyrosine kinases has a double effect The tyrosine kinase activity undergoes autoactivation by phosphorylation of Tyr residues localized in or close to the active center (see 8.1.3). In addition, Tyr residues that lie outside the active center are phosphorylated. The phosphotyrosine residues thereby created serve as binding sites for effector molecules next in the sequence of the signal transduction pathway (see Fig. 8.6). 

These examples illustrate the diversity of receptor tyrosine kinase-initiated signal transduction pathways ... 

In addition to receptor tyrosine kinases, the cell also contains a number of tyrosine-specific protein kinases that are not an integral component of transmembrane receptors. These nonreceptor tyrosine kinases are localized in the cytoplasm at least occasionally or they are associated with transmembrane receptors on the cytoplasmic side of the cell membrane. They are therefore also known as cytoplasmic tyrosine kinases. The nonreceptor tyrosine kinases perform essential functions in signal transduction via cytokine receptors (see Chapter 11) and T cell receptors, and in other signaling pathways. 

Intracellular signal transduction employs central switching stations that receive, modulate and transmit signals further. The Ras proteins (also known as p2T proteins) make up a switching station of particular importance for growth and differentiation processes. The Ras proteins process signals received by receptor tyrosine kinases, by receptors with associated tyrosine kinase activity and by G-protein-coupled receptors, and transmit these into the cell interior (Fig. 9.1). 

Collaborative signaling integrin-mediated cell adhesion modulates signal transduction by other receptors (e.g., receptor tyrosine kinases). 

Carpenter G. Receptor tyrosine kinase substrates Src homology domains and signal transduction. 

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