Phosphotyrosine specifies the phosphorylation by protein kinase CK2 of a peptide reproducing the activation loop of the insulin receptor protein tyrosine kinase.
Protein kinase CK2 is a ubiquitous Ser/Thr-specific protein kinase responsible for the phosphorylation of many proteins implicated in signal transduction. It phosphorylates both threonyl and seryl residue(s) of the insulin receptor beta-subunit. In this study, a series of peptides, reproducing all the threonyl sites of the intracellular domain of the insulin receptor that display the consensus sequence for CK2, has been synthesized and used as substrate for purified rat liver CK2. The only peptide readily phosphorylated is the one reproducing the activation loop of the insulin receptor (EIYET1160DYYA), including three tyrosines (Y1158, Y1162 and Y1163) whose phosphorylation through an intermolecular autocatalytic process promotes the activation of the receptor kinase. The phosphorylation efficiency of T1160 is increased almost 20-fold if these three tyrosines are previously phosphorylated. By using variably phosphorylated peptides, the tyrosine mainly responsible for such a hierarchical phosphorylation process has been identified as Y1163. It can be concluded, from these data, that T1160 situated in the activation loop of the insulin receptor, represents an excellent target for CK2, its phosphorylation being triggered by the previous autophosphorylation of the three tyrosyl residues surrounding it, with special reference to Y1163. These data are consistent with the implication of CK2 in the regulation of the activation process of the insulin receptor protein tyrosine kinase.
Marin
O
O
Dipartimento di Chimica Biologica, Università di Padova, Italy.
Meggio
F
F
Perich
J W
JW
Pinna
L A
LA
D000818:Animals; D047390:Casein Kinase II; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*
D004268:DNA-Binding Proteins; D019000:Phosphotyrosine; D011972:Receptor, Insulin; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases