A proline-rich motif in the C terminus of Akt contributes to its localization in the immunological synapse.
The serine/threonine kinases of the Akt/protein kinase B family are regulated in part by recruitment to the plasma membrane, which is accomplished by the binding of an N-terminal PH domain to the phosphatidylinositol 3-kinase products phosphoinositol 3,4,5-trisphosphate and phosphoinositol 3,4-bisphosphate. We have examined Akt localization in a murine T cell clone (D10) before and after stimulation by APC/Ag, and we found that whereas the pleckstrin homology domain is required for plasma membrane recruitment of Akt upon T cell activation, the C terminus of the kinase restricts its cellular localization to the immunologic synapse formed at the site of T cell/APC contact. A recently described proline-rich motif in this region appears to be important for proper localization of full-length Akt. Moreover, a form of Akt in which this motif was mutated acts as a potent dominant negative construct to block T cell activation. Therefore, multiple mechanisms are involved in the proper targeting of Akt during the early events of T cell activation.
Kane
Lawrence P
LP
Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Mollenauer
Marianne N
MN
Weiss
Arthur
A
D020816:Amino Acid Motifs; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D001798:Blood Proteins / Q000302:isolation & purification; D002450:Cell Communication / Q000276:immunology*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010750:Phosphoproteins / Q000302:isolation & purification; D011392:Proline / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D014162:Transfection
D001798:Blood Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C039077:platelet protein P47; D011392:Proline; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt