Receptor protein tyrosine kinases, signal pathways

Photoaffinity Labeling of Receptor Protein Tyrosine Kinases (PTK) and Biomolecular Targets Involved in the Signaling Pathways... 

The coupling of superantigen—major histocompatibility complex class II to T-cell receptor swifdy results in cell-signaling cascades. ° These staphylococcal toxins can increase levels of phosphatidyl inositol from quiescent T cells, such as other mitogens, as well as elicit intracellular Ca movement that activates the protein kinase C (PKC) pathway important for interleukin-2 (IL-2) expression. " IL-2 is intimately linked to T-cell proliferation. In addition to the PKC pathway, the protein tyrosine kinase (PTK) pathway is also activated by superantigens, leading to elevated expression of various proinflammatory cytokines. Staphylococcal superantigens also potently activate transcriptional factors NF-/IB (nuclear factor kappa B) and AP-1 (activator protein-1), which subsequently elicit the synthesis of proinflammatory cytokines. " " ... 

P. Van der Geer, T. Hunter, and R. A. Lindberg. Receptor protein tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol, 10, 251—337, 1994. 

Signal pathways operated by receptor protein tyrosine kinase... 

Figure 3. MAP kinase regulatory pathway. The MAP kinase signaling pathway begins with activation of the receptor tyrosine kinase (RTK) by exogenous signals, such as growth factors and insulin. The signal is then transmitted into the cell via activation of the Raf serine/threonine kinase either directly by the RTK or through the GTP-binding protein, Ras. The signal is then transmitted to the nucleus and to other cytoplasmic proteins via MAPKK and MAPK.

Downstream in the pathway of rescue, PKB effects a number of phosphorylations that prevent apoptosis (Figure 8.17) (see Section 8.2 3.2). It is of interest to note that both growth factor receptors, such as TrkA, and adhesion molecules generate rescue signals through activation of protein tyrosine kinases, and apparently cells require both attachment to extracellular matrix and the presence of a particular growth factor in order not to die. 

Comparison of Signal-Transduction Pathways Downstream of a Protein Tyrosine Kinase Receptor in Species of Three Separate Phyla... 

Fig. 5.5. General functions of transmembrane receptors. Extracellular signals convert the transmembrane receptor from the inactive form R to the active form R. The activated receptor transmits the signal to effector proteins next in the reaction sequence. Important effector reactions are the activation of heterotrimeric G-proteins, of protein tyrosine kinases and of protein tyrosine phosphatases. The tyrosine kinases and tyrosine phosphatases may be an intrinsic part of the receptor or they may be associated with the receptor. The activated receptor may also include adaptor proteins in the signaling pathway or it may induce opening of ion channels.

Starting from an activated receptor tyrosine kinase, further conduction of the signal takes place with the help of specific protein-protein interactions between the activated receptor and one or more effector proteins next in the sequence. In many cases, the effector molecules pass the signal on to other proteins of the signaling pathway, forming chains of signal proteins in sequence. Specific protein-protein interactions are the... 

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. 

Leptin makes the cells of liver and muscle more sensitive to insulin. One hypothesis to explain this effect suggests cross-talk between the protein tyrosine kinases activated by leptin and those activated by insulin (Fig. 23-35) common second messengers in the two signaling pathways allow leptin to trigger some of the same downstream events that are triggered by insulin, through insulin receptor substrate-2 (IRS-2) and phos-phoinositide 3-kinase (PI-3K) (Chapter 12). 

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