Protein kinases oncogenes

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Zhao, X., Singh, B and Arlinghaus, R. B. (1991). Inhibition of c-mos protein kinase blocks mouse zygotes at the pronuclei stage. Oncogene 6 1423-1426. 

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Protein kinase B, or Akt, was discovered as the product of an oncogene of the acutely transforming retrovirus AKT8, causing T-cell lymphomas in mice. It encodes a fusion product of a cellular serine/threonine protein kinase and the viral structural protein Gag. This kinase is similar to both protein kinase Ce (PKCe 73% identity to the catalytic domain) and protein kinase A (PKA 68%). It differs from other protein kinases in that it contains a pleckstrin homology (PH) domain, which allows it to bind to polyphosphoinositide head groups (and also to G-protein fly subunits). To date, three subtypes have been identified a, (3, and y, all of which show a broad tissue distribution. It... 

The importance of FAK is underlined by the finding that cells expressing a constitutively active form survive in suspension even though they are homeless. Here, the protein kinase is active regardless of the failure to make contact with an extracellular matrix. Rescue from apoptosis also occurs when cells express constitutively activated oncogenic forms of Ras or Src and thus activate Plj-kinase and the MAP kinase pathway. Unlike FAK, these not only prevent apoptosis but also promote proliferative signals that result in tumor formation. 

For example, c-Fos is heavily phosphorylated on a series of serine residues in the C-terminal domain of the protein by several types of protein kinases. The likely functional importance of these phosphorylation sites is indicated by the fact that the difference between c-Fos (the normal cellular form of the protein) and v-Fos (the viral oncogene product) is a frameshift mutation in the v-Fos protein, which obliterates the phosphorylated serine residues. It is speculated that the loss of these phosphorylation sites removes one mechanism by which the cell can regulate the protein, thereby leading to cellular transformation. 

Benhar, M. et al., Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensitization to genotoxic stress, Mol. Cell. Biol., 21, 6913, 2001. 

AKT-1 kinase (also called protein kinase B or PKBa) is a serine/threonine kinase belonging to the AGC kinase family [1], AKT was identified from a viral oncogene, v-akt, found in tumor lines established from spontaneous thymomas found in AKR mice [2]. Subsequently, two more AKT isoforms, AKT-2 (or PKB(3) and AKT-3 (or PKBy) have been identified [3]. Reviews exist detailing the structural and cell biology of AKT and the reader is referred to these for further information [4,7,12]. 

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