Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Cell Biol. 165 (5): 641-652

Copyright © 2004 by the Rockefeller University Press.


Article

Trafficking of Lyn through the Golgi caveolin involves the charged residues on {alpha}E and {alpha}I helices in the kinase domain

Kousuke Kasahara, Yuji Nakayama, Kikuko Ikeda, Yuka Fukushima, Daisuke Matsuda, Shinya Horimoto, , and Naoto Yamaguchi

Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan

Address correspondence to Naoto Yamaguchi, Dept. of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan. Tel./Fax: 81-43-226-2868. email: nyama{at}p.chiba-u.ac.jp

Abstract: 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 {alpha}E helix, and Asp498 and Asp499 on {alpha}I 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.

Key Words: FRAP; intracellular localization; secretory pathway; open conformation; Src-family tyrosine kinase


Abbreviations used in this paper: BFA, brefeldin A; CHX, cycloheximide; GalT, ß-1,4-galactosyltransferase; NEM, N-ethyl-maleimide; SH, Src homology.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Activation of the Prereplication Complex Is Blocked by Mimosine through Reactive Oxygen Species-activated Ataxia Telangiectasia Mutated (ATM) Protein without DNA Damage.
S. Kubota, Y. Fukumoto, K. Ishibashi, S. Soeda, S. Kubota, R. Yuki, Y. Nakayama, K. Aoyama, N. Yamaguchi, and N. Yamaguchi (2014)
J. Biol. Chem. 289, 5730-5746
   Abstract »    Full Text »    PDF »
The iodide-transport-defect-causing mutation R124H: a {delta}-amino group at position 124 is critical for maturation and trafficking of the Na+/I- symporter.
V. Paroder, J. P. Nicola, C. S. Ginter, and N. Carrasco (2013)
J. Cell Sci. 126, 3305-3313
   Abstract »    Full Text »    PDF »
Phosphorylation of KRAB-associated Protein 1 (KAP1) at Tyr-449, Tyr-458, and Tyr-517 by Nuclear Tyrosine Kinases Inhibits the Association of KAP1 and Heterochromatin Protein 1{alpha} (HP1{alpha}) with Heterochromatin.
S. Kubota, Y. Fukumoto, K. Aoyama, K. Ishibashi, R. Yuki, T. Morinaga, T. Honda, N. Yamaguchi, T. Kuga, T. Tomonaga, et al. (2013)
J. Biol. Chem. 288, 17871-17883
   Abstract »    Full Text »    PDF »
Nuclear ErbB4 signaling through H3K9me3 is antagonized by EGFR-activated c-Src.
K. Ishibashi, Y. Fukumoto, H. Hasegawa, K. Abe, S. Kubota, K. Aoyama, S. Kubota, Y. Nakayama, and N. Yamaguchi (2013)
J. Cell Sci. 126, 625-637
   Abstract »    Full Text »    PDF »
c-Src but Not Fyn Promotes Proper Spindle Orientation in Early Prometaphase.
Y. Nakayama, Y. Matsui, Y. Takeda, M. Okamoto, K. Abe, Y. Fukumoto, and N. Yamaguchi (2012)
J. Biol. Chem. 287, 24905-24915
   Abstract »    Full Text »    PDF »
The Lyn kinase C-lobe mediates Golgi export of Lyn through conformation-dependent ACSL3 association.
Y. Obata, Y. Fukumoto, Y. Nakayama, T. Kuga, N. Dohmae, and N. Yamaguchi (2010)
J. Cell Sci. 123, 2649-2662
   Abstract »    Full Text »    PDF »
Differential trafficking of Src, Lyn, Yes and Fyn is specified by the state of palmitoylation in the SH4 domain.
I. Sato, Y. Obata, K. Kasahara, Y. Nakayama, Y. Fukumoto, T. Yamasaki, K. K. Yokoyama, T. Saito, and N. Yamaguchi (2009)
J. Cell Sci. 122, 965-975
   Abstract »    Full Text »    PDF »
Microtubule-mediated Src Tyrosine Kinase Trafficking in Neuronal Growth Cones.
B. Wu, B. Decourt, M. A. Zabidi, L. T. Wuethrich, W. H. Kim, Z. Zhou, K. MacIsaac, and D. M. Suter (2008)
Mol. Biol. Cell 19, 4611-4627
   Abstract »    Full Text »    PDF »
Regulation of caveolin-1 membrane trafficking by the Na/K-ATPase.
T. Cai, H. Wang, Y. Chen, L. Liu, W. T Gunning, L. E. M. Quintas, and Z.-J. Xie (2008)
J. Cell Biol. 182, 1153-1169
   Abstract »    Full Text »    PDF »
Interaction between Hck and HIV-1 Nef negatively regulates cell surface expression of M-CSF receptor.
M. Hiyoshi, S. Suzu, Y. Yoshidomi, R. Hassan, H. Harada, N. Sakashita, H. Akari, K. Motoyoshi, and S. Okada (2008)
Blood 111, 243-250
   Abstract »    Full Text »    PDF »
Src Signaling Regulates Completion of Abscission in Cytokinesis through ERK/MAPK Activation at the Midbody.
K. Kasahara, Y. Nakayama, Y. Nakazato, K. Ikeda, T. Kuga, and N. Yamaguchi (2007)
J. Biol. Chem. 282, 5327-5339
   Abstract »    Full Text »    PDF »
PRA1 promotes the intracellular trafficking and NF-{kappa}B signaling of EBV latent membrane protein 1.
H.-P. Liu, C.-C. Wu, and Y.-S. Chang (2006)
EMBO J. 25, 4120-4130
   Abstract »    Full Text »    PDF »
Expression and muscarinic receptor coupling of Lyn kinase in cultured human airway smooth muscle cells.
T. Pertel, D. Zhu, R. A. Panettieri, N. Yamaguchi, C. W. Emala, and C. A. Hirshman (2006)
Am J Physiol Lung Cell Mol Physiol 290, L492-L500
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882