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Tyrosine-specific protein kinases are, like serine/threonine-specific kinases, used in [signal transguction]?. They act primarily as [growth factor]? receptors, for example, the [platlet derived growth factor]?, [epidermal growth factor]?, [transforming growth factor]?, insulin and insulin-like growth factor, interleukin?es, and [tumor necrosis factor]?. Receptor tyrosine kinasesThese kinases consist of a transmembrane receptor with a tyrosine kinase domain integrated in the cytoplasmic? domain. They play an important role in the regulation of [cell division]?, [cell differentiation]?, and morphogenesis. There are more than 50 known receptor tyrosine kinases in mammals. StructureThe extracellular domain serves as the ligand receptor. It can be a sepatate unit that is attached to the rest of the receptor via a [disulfide bond]?. The same mechanism can be used to bind two receptors together to form a homo- or heterodimer. The transmembrane element is a single [α helix]?. The intracellular or cytoplasmic domain contains the (highly conserved) kinase activity, as well as several regulatory functions. RegulationThe ligand binding causes two reactions: # The dimerisation of two monomeric receptor kinases, or the stabelization of a loose dimer. Many ligands of receptor tyrosine kinases are multivalent?. Some tyrosine receptor kinases (e.g., the [platelet derived growth factor]? receptor) can build heterodimers with other similar, but not equal kinases of that subfamily, allowing a much varied response to the extracellular signal. # The 'trans''-autophosphorylation (phosphorylation? by the other kinase in the dimer?) of the kinase. The autophosphorylation causes the two subdomains of the intrinsic? kinase to shift, opening the kinase domain for ATP binding. In the inactive form, the kinase subdomains are aligned in a way that ATP cannot reach the [catalytic center]? of the kinase. When several amino acids suited for phosphorylation are present in the kinase domain (e.g., the insulin-like growth factor receptor), the activity of the kinase can increase with the number of phosphorylated amino acids; in this case, the first phosphorylation is said to be a cis-autophosphorylation, switching the kinase form "off" to "standby". Signal transductionThe active tyrosine kinase phosphorylates specific target proteins, which are often enzymes themselves. An important target is the [ras protein]? signal transduction chain. |
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