title: Functionally distinct serine phosphorylation sites of p36, the cellular substrate of retroviral protein kinase; differential inhibition of reassociation with p11.
abstract: P36 was originally defined as the major cytoplasmic target of retrovirally coded tyrosine-kinases. While recently much has been learned about its biochemistry, the functional importance of its tyrosine and serine phosphorylation has not been approached. As p36 is now understood as a multi-ligand protein its in vitro phosphorylation by three different serine/threonine kinases was followed. Monomeric p36 is a much better substrate than the complex containing two copies each of p36 and p11 (protein I). All p36 phosphorylation sites occur within the amino-terminal 29 residues specifically released by mild proteolysis. As this region harbors an important interaction site for p11 the reduced phosphorylation of p36 in the protein I complex results most likely from a lowered accessibility. Phosphorylation of p36 is serine specific. Reconstitution experiments define at least two functionally distinct sites. One product of protein kinase C reconstitutes with p11 to protein I, while this complex formation normal for p36 is observed neither for the second phosphorylation product nor for the derivatives resulting from phosphorylation by calmodulin or cAMP dependent kinases. The results lend direct support to the hypothesis that phosphorylation of p36 can modulate one of its molecular functions. Obvious implications for other Ca2+-dependent lipid binding proteins are discussed.
mesh_terms: D000596:Amino Acids / Q000032:analysis; D046911:Macromolecular Substances; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012190:Retroviridae / Q000378:metabolism*; D012694:Serine; D013379:Substrate Specificity; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D046911:Macromolecular Substances; D014764:Viral Proteins; D012694:Serine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases