Subcellular localization analysis of the closely related Fps/Fes and Fer protein-tyrosine kinases suggests a distinct role for Fps/Fes in vesicular trafficking.
The subcellular localizations of the Fps/Fes and closely related Fer cytoplasmic tyrosine kinases were studied using green fluorescent protein (GFP) fusions and confocal fluorescence microscopy. In contrast to previous reports, neither kinase localized to the nucleus. Fer was diffusely cytoplasmic throughout the cell cycle. Fps/Fes also displayed a diffuse cytoplasmic localization, but in addition it showed distinct accumulations in cytoplasmic vesicles as well as in a perinuclear region consistent with the Golgi. This localization was very similar to that of TGN38, a known marker of the trans Golgi. The localization of Fps/Fes and TGN38 were both perturbed by brefeldin A, a fungal metabolite that disrupts the Golgi apparatus. Fps/Fes was also found to colocalize to various extents with several Rab proteins, which are members of the monomeric G-protein superfamily involved in vesicular transport between specific subcellular compartments. Using Rabs that are involved in endocytosis (Rab5B and Rab7) or exocytosis (Rab1A and Rab3A), we showed that Fps/Fes is localized in both pathways. These results suggest that Fps/Fes may play a general role in the regulation of vesicular trafficking.
Zirngibl
R
R
Cancer Research Laboratories, Queen's University, Kingston, Ontario K7L 3N6, Canada.
Schulze
D
D
Mirski
S E
SE
Cole
S P
SP
Greer
P A
PA
D000818:Animals; D019556:COS Cells / Q000166:cytology / Q000378:metabolism; D002451:Cell Compartmentation / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism* / Q000648:ultrastructure; D015681:Fusion Proteins, gag-onc / Q000378:metabolism*; D006023:Glycoproteins; D006056:Golgi Apparatus / Q000378:metabolism; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D021381:Protein Transport / Q000502:physiology*; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000378:metabolism
D015681:Fusion Proteins, gag-onc; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases; C068415:v-fps oncogene protein, Fujinami sarcoma virus; D020691:rab GTP-Binding Proteins