Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA-encoded protein.
The c-erbA proto-oncogene encodes a nuclear receptor for thyroid hormone (T3), which is believed to stimulate transcription from specific target promoters upon binding to cis-acting DNA sequence elements. The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes a ligand-independent version of this nuclear receptor. The v-erbA product inhibits terminal differentiation of avian erythroblasts, presumably by affecting the transcription of specific genes. We show here that the c-erbA-encoded nuclear receptor (p46c-erbA) is phosphorylated on serine residues on two distinct sites. One of these sites, defined by the limit tryptic phosphopeptide 28SSQCLVK, is retained on the v-erbA-encoded P75gag-v-erbA protein. This site is located in the amino-terminal domain of these molecules, 21 amino acids upstream of the DNA-binding region. Phosphorylation of this site in both p46c-erbA and P75gag-v-erbA is enhanced 10-fold following treatment of cells with activators of either protein kinase C or cAMP-dependent protein kinase. Since cAMP-dependent protein kinase phosphorylates both p46c-erbA and P75gag-v-erbA in vitro at the same site as that observed in vivo, at least part of the cAMP-dependent phosphorylation of erbA molecules in cells could result from direct phosphorylation by this enzyme. The possible role phosphorylation may play in the function of the erbA-encoded transcriptional factors is discussed.
D001355:Alpharetrovirus / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002642:Chick Embryo; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D018774:Oncogene Proteins v-erbA; D010446:Peptide Fragments / Q000378:metabolism; D010449:Peptide Mapping; D010766:Phosphorylation; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*
D018774:Oncogene Proteins v-erbA; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D011988:Receptors, Thyroid Hormone; D012191:Retroviridae Proteins; D011494:Protein Kinases; D011493:Protein Kinase C