A SERINE-KINASE ASSOCIATED WITH THE P127-L(2)GL TUMOR-SUPPRESSOR OF DROSOPHILA MAY REGULATE THE BINDING OF P127 TO NONMUSCLE MYOSIN-II HEAVY-CHAIN AND THE ATTACHMENT OF P127 TO THE PLASMA-MEMBRANE

The p127 tumour suppressor protein encoded by the lethal(2)giant larva e, [l(2)gl] gene of Drosophila melanogaster is a component of a cytosk eletal network distributed in both the cytoplasm and on the inner face of the plasma membrane. The p127 protein forms high molecular mass co mplexes consisting mainly of homo-oligomerized p127 molecules and at l east ten additional proteins. One of these proteins has been recently identified as nonmuscle myosin type II heavy chain. To determine the f unctional interactions between p127 and other proteins present in the p127 complexes, we analyzed p127 for posttranslational modifications a nd found that p127 can be phosphorylated at serine residues. In this r eport we describe the characteristics of a serine kinase which is asso ciated with p127, as judged by its recovery in p127 complexes purified by either gel filtration or immune-affinity chromatography. This kina se phosphorylates p127 in vitro and its activation by supplementing AT P results in the release of p127 from the plasma membrane. Moreover, s imilar activation of the kinase present in immune-purified p127 comple xes dissociates nonmuscle myosin II from p127 without affecting the ho mo-oligomerization of p127. This dissociation can be inhibited by stau rosporine and a 26mer peptide covering amino acid positions 651 to 676 of p127 and containing five serine residues which are evolutionarily conserved from Drosophila to humans. These results indicate that a ser ine-kinase tightly associated with p127 regulates p127 binding with co mponents of the cytoskeleton present in both the cytoplasm and on the plasma membrane.