The ability of RME 8 to associate with PI(3)P and early endosomes is largely abolished when residues Lys17, Trp20, Tyr24, or Arg26 are mutated resulting in diffuse cytoplasmic localization of RME 8 while maintaining the ability to interact with Hsc70. We also provide evidence that RME 8 PI(3)P binding regulates the early endosomal clathrin dynamics and alters the steady state localization of the cation independent mannose 6 phosphate receptor.In addition, once a phosphorylation deficient variant (S58A) targets MTMR2 to Rab5 positive endosomes and depleting PI(3)P, it results in increased endosomal signaling, such as a significant increase in ERK1/2 activation. Using in vitro kinase assays, cellular MAPK inhibitors, siRNA knockdown and a phosphospecific Ser58 antibody, we provide evidence that ERK1/2 is the kinase responsible for phosphorylating MTMR2 at position Ser58, which suggests that the endosomal targeting of MTMR2 is regulated through an ERK1/2 negative feedback mechanism.Taken together, our results suggest a model in which the localization of RME 8 to endosomal compartments is spatially mediated by PI(3)P binding and temporally regulated by MTMR2 activity and compartmentalization of MTMR2 and potential subsequent effects on endosome maturation and endosome signaling are dynamically regulated through MAPK mediated differential phosphorylation events..
Investigation by Fulmore police stationWest side based Minerva Athletic Club owner Lawrence ManganoWest side based Minerva Athletic Club owner Lawrence ManganoWest side mobster Lawrence Mangano owner of the Minerva Athletic Club which was raided 7 September 1928 the next day was bombed the house of Des Plaines street police station captain Luke Garrick42 gang member Giancana27 September 1928 explodes for the second time in 11 days a bomb near the ice salon of Sam Giancana’s father. Police suspect it is revenge for the murder of Edward Divis (when was he killed then?? And is the name right?) a gangster boss in West Chicago and suspected were Sam Giancana and Dominic Caruso. West side based William “Klondike” O’Donnell clash with George “Red” Barker George “Red” Barker3 September 1928 was garage attendant Albert Pratt (30) shot and killedGeorge “Red” Barker27 October 1928 were George “Red” Barker, William Clifford and Michael Reilly arrested in San Francisco for the murder of Chicago garage attendant Albert PrattCoal teamsters local 704 president James “Lefty” LynchAt the next meeting of the joint council, Red Barker and Murray Humphreys appeared at the door with a dozen heavily armed Capone torpedoes.