The TK group
In metazoans, tyrosine phosphorylation plays an essential role in inter- and intracellular signal transduction (organ development, tissue homeostasis, transcriptional control, proliferative vs. differentiation decisions, cell shape and cell motility). Abnormalities in tyrosine phosphorylation are closely related to oncogenic transformation.
Members of the TK group specifically phosphorylate tyrosine residues and are therefore distinct from dual specificity kinases which phosphorylate serine/threonine in addition to tyrosine. Many TKs have well-established roles in metazoans, for example some TKs are proto-oncogenes such as the Abelson kinase (c-Abl). c-Abl is constitutively activated when translocated to the genetic locus of the breakpoint cluster region (leading to the Bcr/Abl fusion gene), thus forming the causative pathogenic event for the development of chronic myeloid leukaemia (CML). Other TKs are part of simple yet important signalling cascades (JAK kinases in the JAK-STAT pathway), are important for blood glucose homeostasis (insulin receptor), and for embryonic development or maintenance of stem cells (e.g. epidermal and vascular growth factor receptors). Despite these well established roles in animals, and the absence of TKs in fungi, a number of putative TKs have been found in the alga Chlamydomonas, Phytophora and in Entamoeba histolytica. With the HMM library we have also found putative TKs in these organisms and in photosynthetic organisms, suggesting that TKs may have been present in ancestral eukaryotes and been lost on multiple occasions. In fact, tyrosine phosphorylated proteins were biochemically characterised in plants and algae many years ago.
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The kinase inhibitor imatinib--an immunosuppressive drug?
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Mol Biol Evol.
The JAK-STAT signaling pathway: input and output integration.
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VEGF receptor signalling - in control of vascular function.
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