ABSTRACT
The EGF receptor is a transmembrane glycoprotein of Mr 170,000 (1). The binding of EGF to the receptor results in the dimer formation, an increase in the tyrosine kinase activity of the cytoplasmic domain, and the autophosphorylation of the carboxyl-terminal tyrosine at residues 992, 1068, 1086, 1148, and 1173 (1). Once activated, the receptor ini tiates a series of signal-transduction events through the interaction of phosphorylated tyrosine residues and the proteins of SH2 family. Be side tyrosine phosphorylation, the EGF-activated receptors are abundant for the serine/threonine phosphorylation (Thr669, Ser671, Ser967, Ser971, Seri002, and Seri046/1047), by which signaling functions are attenuated (2,3). Various protein kinases are considered to be involved in such phosphorylation (Table 1) (4). Thr669 is phosphorylated by two growth factor-stimulated protein kinases: a MAP kinase and an EGF receptor Thr669 (ERT) kinase (5,6). It is known that casein kinase II (CKII), p34cdc2 and Ca2+/calmodulin-dependent kinase (CaMK) phosphorylate Ser671, Serl002, and Serl046/1047 in vitro, respectively (2,3).
