TY - JOUR
T1 - Requirement of the SH4 and tyrosine-kinase domains but not the kinase activity of Lyn for its biosynthetic targeting to caveolin-positive Golgi membranes
AU - Ikeda, Kikuko
AU - Nakayama, Yuji
AU - Ishii, Mayuko
AU - Obata, Yuuki
AU - Kasahara, Kousuke
AU - Fukumoto, Yasunori
AU - Yamaguchi, Naoto
N1 - Funding Information:
We are grateful to Dr. Tadashi Yamamoto (The University of Tokyo) for the plasmid. This work was supported in part by grants-in-aid for Scientific Research and Global COE Program (Global Center for Education and Research in Immune Regulation and Treatment) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and research grants from the Hamaguchi Foundation for the Advancement of Biochemistry and the Suzuken Memorial Foundation. K.I. and Y.O. are Global COE Research Assistants.
PY - 2009/10
Y1 - 2009/10
N2 - Background: The Src-family non-receptor-type tyrosine kinase Lyn, which is often associated with chemotherapeutic resistance in cancer, localizes not only to the plasma membrane but also Golgi membranes. Recently, we showed that Lyn, which is synthesized in the cytosol, is transported from the Golgi to the plasma membrane along the secretory pathway. However, it is still unclear how Golgi targeting of newly synthesized Lyn is regulated. Methods: Subcellular localization of Lyn and its mutants was determined by confocal microscopy. Results: We show that the kinase domain, but not the SH3 and SH2 domains, of Lyn is required for the targeting of Lyn to the Golgi, whereas the N-terminal lipids of the Lyn SH4 domain are not sufficient for its Golgi targeting. Although intact Lyn, which colocalizes with caveolin-positive Golgi membranes, can traffic toward the plasma membrane, kinase domain-deleted Lyn is immobilized on caveolin-negative Golgi membranes. General significance: Besides the SH4 domain, the Lyn kinase domain is important for targeting of newly synthesized Lyn to the Golgi, especially caveolin-positive transport membranes. Our results provide a novel role of the Lyn catalytic domain in the Golgi targeting of newly synthesized Lyn in a manner independent of its kinase activity.
AB - Background: The Src-family non-receptor-type tyrosine kinase Lyn, which is often associated with chemotherapeutic resistance in cancer, localizes not only to the plasma membrane but also Golgi membranes. Recently, we showed that Lyn, which is synthesized in the cytosol, is transported from the Golgi to the plasma membrane along the secretory pathway. However, it is still unclear how Golgi targeting of newly synthesized Lyn is regulated. Methods: Subcellular localization of Lyn and its mutants was determined by confocal microscopy. Results: We show that the kinase domain, but not the SH3 and SH2 domains, of Lyn is required for the targeting of Lyn to the Golgi, whereas the N-terminal lipids of the Lyn SH4 domain are not sufficient for its Golgi targeting. Although intact Lyn, which colocalizes with caveolin-positive Golgi membranes, can traffic toward the plasma membrane, kinase domain-deleted Lyn is immobilized on caveolin-negative Golgi membranes. General significance: Besides the SH4 domain, the Lyn kinase domain is important for targeting of newly synthesized Lyn to the Golgi, especially caveolin-positive transport membranes. Our results provide a novel role of the Lyn catalytic domain in the Golgi targeting of newly synthesized Lyn in a manner independent of its kinase activity.
KW - Golgi caveolin
KW - Kinase domain
KW - Lipid modification
KW - Lyn
KW - Src-family tyrosine kinase
KW - Targeting
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U2 - 10.1016/j.bbagen.2009.07.009
DO - 10.1016/j.bbagen.2009.07.009
M3 - Article
C2 - 19619611
AN - SCOPUS:69949106681
SN - 0304-4165
VL - 1790
SP - 1345
EP - 1352
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 10
ER -