Trafficking of Lyn through the Golgi caveolin involves the charged residues on alphaE and alphaI helices in the kinase domain.
Src-family kinases, known to participate in signaling pathways of a variety of surface receptors, are localized to the cytoplasmic side of the plasma membrane through lipid modification. We show here that Lyn, a member of the Src-family kinases, is biosynthetically transported to the plasma membrane via the Golgi pool of caveolin along the secretory pathway. The trafficking of Lyn from the Golgi apparatus to the plasma membrane is inhibited by deletion of the kinase domain or Csk-induced "closed conformation" but not by kinase inactivation. Four residues (Asp346 and Glu353 on alphaE helix, and Asp498 and Asp499 on alphaI helix) present in the C-lobe of the kinase domain, which can be exposed to the molecular surface through an "open conformation," are identified as being involved in export of Lyn from the Golgi apparatus toward the plasma membrane but not targeting to the Golgi apparatus. Thus, the kinase domain of Lyn plays a role in Lyn trafficking besides catalysis of substrate phosphorylation.
Kasahara
Kousuke
K
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
Nakayama
Yuji
Y
Ikeda
Kikuko
K
Fukushima
Yuka
Y
Matsuda
Daisuke
D
Horimoto
Shinya
S
Yamaguchi
Naoto
N
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001224:Aspartic Acid / Q000378:metabolism; D019556:COS Cells; D021941:Caveolae / Q000201:enzymology* / Q000648:ultrastructure; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D018698:Glutamic Acid; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000906:Antibodies; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D001224:Aspartic Acid; D018698:Glutamic Acid; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases