Requirement of the SH4 and tyrosine-kinase domains but not the kinase activity of Lyn for its biosynthetic targeting to caveolin-positive Golgi membranes

Kikuko Ikeda, Yuji Nakayama, Mayuko Ishii, Yuuki Obata, Kousuke Kasahara, Yasunori Fukumoto, Naoto Yamaguchi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1345-1352
Number of pages8
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

Keywords

  • Golgi caveolin
  • Kinase domain
  • Lipid modification
  • Lyn
  • Src-family tyrosine kinase
  • Targeting

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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