title: Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C adaptor.
abstract: Nef proteins of primate immunodeficiency viruses exert pleiotropic effects, such as enhanced endocytosis of CD4 and MHC-I cell surface molecules, perturbation of signal transduction cascades, and virion infectivity enhancement. Nef function intersects that of a number of cell kinases, including C kinases (PKCs) and Src-family kinases. Here the interaction of HIV-1 Nef with Rack1 (receptor for activated C kinase 1) is reported. Nef binds the Rack1 C-terminal moiety in a yeast two-hybrid system and in cell-free pull-down assays and copurifies with in vitro translated Rack1. Nef and Rack1 partially colocalize on the trans-Golgi network and plasma membranes. The presence of Rack1 doubles Nef phosphorylation by PKCs in vitro. Our data agree with the idea that Rack1 acts as a Nef intracellular docking site, bringing Nef and PKCs together. Other signal transduction or endocytosis proteins, in particular Src-like kinases, might meet Nef by intermediation of the Rack1 adaptor.
authors: Department of Medicine and Surgery, Polo Universitario Ospedale San Paolo, University of Milano, via A. di Rudiní 8, I-20142 Milan, Italy.
authors: A
authors: A
authors: Gallina
authors: F
authors: F
authors: Rossi
authors: G
authors: G
authors: Milanesi
mesh_terms: D000818:Animals; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D000075370:Receptors for Activated C Kinase; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D015693:Gene Products, nef; D010455:Peptides; D000075370:Receptors for Activated C Kinase; C070301:peptide I; D011493:Protein Kinase C