Protein Tyrosine Phosphorylation

Phosphorylated tyrosyl residues in proteins are quantitatively much less abundant in normal cells than phosphoserines or phosphothreonines, yet tyrosine phosphorylation plays a crucial role in cellular regulation, including cell transformation by viral oncogenes and the action of growth factors (Hunter and Cooper, 1985). The role of tyrosine phosphorylation in signal transduction has been neglected for some time in mature neurons, which are postmitotic cells, although the situation has changed dramatically over the past few years. For example, it has been discovered that receptors for neurotrophic factors, the chief example being nerve growth factor (NGF), are transmembrane protein-tyrosine kinases (PTKs) (Ip and Yancopoulos, 1994). In addition, molecular cloning techniques have allowed the identification of many protein-tyrosine kinases and phosphatases that are exclusively or preferentially expressed in nerve cells, in vertebrates as well as in Drosophila . Several PTKs and proteintyrosine phosphatases (PTPases) are critical in the regulation of neural differentiation, neurite growth, and pathfinding (Temple and Qian, 1995; Tessier-Lavigne, 1995).