Advanced Molecular Genetics-Biology 566 Signaling Pathways Operated by non-Receptor Protein Tyrosine Kinases
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Non-receptor protein Tyrosine Kinases

"Examples of the class of receptors that recruit non-receptor PTKs include those that mediate immune and inflammatory responses:

- The T-lymphocyte receptor (TCR) is involved in detection of foreign antigens, presented together with the major histocompatibility complex (MHC). Subsequently it regulates the clonal expansion of T cells.

- TheThe B lymphocyte receptor for antigen is important in the first line of defence against infection by micro-organisms.

- The interleukin-2 receptor (IL-2R). The cytokine IL-2, secreted by a subset of T-helper cells, enhances the proliferation of activated T- and B-cells, increases the cytolytic activity of natural killer (NK) cells and the secretion of IgG. (Pathway blocked by cyclosporin)

- Immunoglobulin receptors, such as the high affinity receptor for IgE (IgE-R), presents on mast cells and blood-born basophills. This plays an important role in hypersensitivity and the initiation of acute inflammatory responses. (Food allergies)

- Erythropietin receptors. The cytokine erythropoietin plays an important role in the final stage of maturation of erythroid cells into mature red blood cells. For this reason it has been used by athletes to boost their performance in endurance sports such as cycling. The erythropoietin receptor is present on a number of cell types in addition to erythroid progenitor cells, suggesting that erythropoietin may have specific effects on other tissues, still to be discerned.

-prolactin receptors. The pituitary hormone prolactin plays a pivotal role in the refulation of lactation. In addition, it has been implicated in modulation of immune responses. For instance, it regulates the level of NK-mediated cytotoxicity. It has also gained attention as a potential male contraceptive."

Activation and inactivation of non-receptor protein tyrosine kinases

Example Pathways

Clonal expansion of naive T-lymphocytes

The IgE receptor and a signal for exocytosis

The IgE receptor aggregation signals the immediate secretion of preformed products stored in secretory granules such as histamine, protoglycans, neutral proteases, acid hydrolases. Over the course of hours the cells synthesize and secrete cytokines and inflammatory mediators.

Lipid Rafts

Plasma membranes are heterogeneous and contain microdomains for lipid composition and receptors, especially in T and B lymphocytes and mast cells. Rafts are a way of concentrating receptors, the lipids and lipid tethered proteins together to provide the elements needed to activate secondary signals.

Activation of STATS by the interferon receptor

Interferons ar a group of cytokines known for their antiviral properties. They are divided into two groups, the alpha and beta (type 1 IFN) and the gamma (type 2 IFN).