Oncogene Characterization and Mode of Action

Half of the products of oncogenes are protein kinases, mostly of the tyrosine type. This finding was of fundamental importance because it revealed that abnormal phosphorylation of a number of proteins could explain, at least in part, various effects of transformation. The critical cell proteins whose abnormal phosphorylation presumably leads to transformation are still to be defined. However, they include vinculin, which is a protein found in focal adhesion plaques (structures involved in intercellular adhesions). The abnormal phosphorylation of vinculin in focal adhesion plaques could explain the tendency of cells to become round and 

Certain glycolytic enzymes appear to be target proteins for protein-tyrosine kinases. They may be responsible for the increased rate of glycolysis in transformed cells. The protein component of ion pumps may also be involved activation of Na+/H+ antiport systems causing mild alkalinization of the cells may play a role in stimulating mitosis. 

A recent finding in a number of laboratories is that phosphotyrosine (SI) is the produce of oncogene protein kinase this has led to the postulation that phosphorylation of tyrosine might be essential for cell transformation. The amount of phosphotyrosine in most cells is low. It is usually elevated in cells transformed by oncogenes, although the amount is still relatively small, amounting to 1% of the total phosphoamino acids (mainly phosphoserine and phosphothreonine). Certain receptors found in both normal and transformed cells have protein tyrosine kinase activities that are stimulated by interaction with their ligands. 

Among the modes of myc activation are two modes (A3) involving rearrangement close to the gene retroviral insertion in the murine T and avian B lymphomas 

The types of studies mentioned here represent a new concept for suppressor gene inactivation during a preneoplastic stage progressing toward malignancy. 

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