General Classification and Function of Protein Kinases

Hie first protein kinase obtained in a purified form was the Ser/Thr-specific phospho-rylase kinase of muscle, in 1959 (Krebs et al., 1959). With the discovery of the Tyr-specific protein kinases (Erikson et al., 1979), the Ser/Thr-specific protein kinases were joined by another extensive class of protein kinases of regulatory importance, to which a central function in growth and differentiation processes was soon attributed. At present, several hrmdred different protein kinases are known in mammals, most of which are Ser/Thr- or Tyr-specific. In addition, there are some protein kinases that phospho-rylate other amino acids (review Hrmter, 1991). 

Based on the nature of the acceptor amino acids, four classes of protein kinases can be distinguished (Fig. 7.1)  

Whilst comprehensive data are available on structure and fimction of the Ser/Thr- and Tyr-specific protein kinases, both the other families of protein kinases are incompletely characterized. 

In the sequence of protein kinases, a homologous catalytic domain can be identified, that includes ca. 270 amino acids. Based on the sequence of the catalytic domain, it is possible to differentiate between Ser/lhr- and Tyr-specific protein kinases. Furthermore, homology considerations enable identification of subfamilies within both the larger families of Ser/lhr- and Tyr-specific protein kinases. 

Protein phosphorylation by protein kinases is a general and versatile tool in the cell, with the fimction of a switch in signaling pathways. Examples of cellular activities regulated by protein kinases are diverse, affecting practically all the cell s performance. Protein phosphorylation is foimd in  

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