ABSTRACT
Protein kinases are enzymes characterized by the presence of a conserved kinase domain that catalyzes the phosphorylation of proteins on tyrosine residues (tyrosine kinases) or serine and threonine residues (serine/threonine kinases). Kinase domains typically occur fused to other domains that serve to mediate interactions with other proteins, localize the kinase domain to specific cellular compartments, or regulate the enzymatic activity of the kinase domain. Protein kinases are either entirely cytoplasmic or, in the case of the receptor kinases, consist of an extracellular region and a single membrane-spanning domain, in addition to a cytoplasmic segment containing the kinase domain. With few exceptions, the known receptor kinases are tyrosine kinases. Their extracellular regions consist of various combinations of protein modules, while their cytoplasmic domains contain the highly conserved kinase domain, which is flanked by a juxtamembrane region and a carboxy-terminal tail. Receptor tyrosine kinases are classified into families based on the similarities in their cytoplasmic domains and the domain structure of their extracellular regions. Single or multiple Ig domains are present in the extracellular regions of many families of receptor kinases (van der Geer et al., 1994). The Ig superfamily of kinases comprises the platelet-derived growth factor (PDGF) receptor family, the fibroblast growth factor (FGF) receptor family, the nerve growth factor (NGF) receptor (Trk) family, the Eph family, the Axl family, the Ror family, the Tie family, and the Klg family. In this chapter, the Eph family is included in the Ig superfamily, even though it is difficult to determine unequivocally, on the basis of sequence information alone, whether an Ig domain is indeed present at the amino terminus of the Eph receptors (O’Bryan et al., 1991; Connor and Pasquale, 1995).
