Receptor tyrosine kinases mechanisms

LiNASSiER c, PIERRE M, LE PECQ J B and PIERRE J (1990) Mechanism of action in NIH-3T3 cells of genistein, an inhibitor of EGF receptor tyrosine kinase activity. Biochem Pharmacol. 39 (1) 187-93. 

Mohammadi, M., Schlessinger, J., and Hubbard, S. R., Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism, Cell, 86, 577-578, 1996. 

There are also monomeric G-proteins. Just like the trimeric G-pro-teins, they are involved as signal relays and timers. The Ras superfamily relays signals from receptor tyrosine kinases to downstream elements that eventually regulate transcription. Rho and Rac relay signals from cell-surface receptors to the cytoskeleton, while Rab regulates intracellular transport of vesicles. Regardless of what they do, they use the timer mechanism provided by the G-protein. Three-letter acronyms (TLA), such as Ras, Rho, and Rab, are difficult to remember, sometimes even when you know what the letters stand for. Unfortunately, there s nothing you can do about this except to memorize them. 

Multiple interactions are also being demonstrated between the traditional second-messenger pathways and the MAPK cascades. Free (3y G protein subunits, generated upon activation of receptors coupled to the G family, lead to activation of the ERK pathway. The mechanism by which this occurs, which may involve an interaction between the subunits and Ras or Raf, is a subject of intensive research (see Ch. 19). In addition, increases in cellular Ca2+ concentrations lead to stimulation of the ERK pathway, apparently via phosphorylation by CaMKs of proteins, for example She and Grb, that link growth factor receptor tyrosine kinases to Ras. Activation of the... 

Mechanisms of Chaperone-Associated Ubiquitination and Degradation of Receptor Tyrosine Kinases... 

Waterman, H., and Y. Yarden. Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases. FEBS Lett. 490 142-52.2001. 

Several cases are described (Cohen et ah, 1995) in which binding of an SH2-containing enzyme to an activated receptor tyrosine kinase leads to increased catalytic activity of the enzyme. Examples are the PI3-kinase and phospholipase Oy. The mechanism of activation is not clear. It is possible, however, that the basis is an allosteric mechanism, as is assumed for activation of Src tyrosine kinase. The Src kinase can be phosphoryla-... 

Mechanism of activation of the epidermal growth factor (EGF) receptor, a representative receptor tyrosine kinase. The receptor polypeptide has extracellular and cytoplasmic domains, depicted above and below the plasma membrane. Upon binding of EGF (circle), the receptor converts from its inactive monomeric state (/eft) to an active dimeric state (right), in which two receptor polypeptides bind noncovalently. The cytoplasmic domains become phosphorylated (P) on specific tyrosine residues (Y) and their enzymatic activities are activated, catalyzing phosphorylation of substrate proteins (S). 

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