title: Endocytosis of cationized ferritin in marginal cells of the stria vascularis is regulated by protein kinase, protein phosphatase, and MEK/ERK and PI3-K signaling pathways.
abstract: OBJECTIVE
  The endocytosis of cationized ferritin (CF) via a clathrin-mediated pathway is regulated by a signaling network.
  
  
  BACKGROUND
  Marginal cells showed the active endocytosis of CF via a clathrin-mediated pathway. The internalization of receptors through the clathrin-mediated pathway is an important regulatory event in signal transduction. Numerous kinases are involved in endocytosis, and each endocytic route is subjected to high-order regulation by cellular signaling mechanisms.
  
  
  METHODS
  CF was infused into the cochlear duct with phorbol 12-myristate 13 acetate, okadaic acid, staurosporin, phenylarsine oxide, PD98059, SB20580 and wortmannin. Endocytic activity was measured at 30 minutes post-infusion by transmission electron microscopy.
  
  
  RESULTS
  The endocytosis of CF was stimulated by a protein kinase C activator (phorbol 12-myristate 13 acetate) and a protein kinase A activator (8-bromoadenosine-3', 5'-cyclic monophosphate). It was inhibited by protein phosphatase inhibitors (okadaic acid and phenylarsine oxide), mitogen-activated protein kinase/extracellular signal-related kinase inhibitors (PD98059 and SB20580), and a phosphatidylinositol 3-kinase inhibitor (wortmannin).
  
  
  CONCLUSIONS
  Our previous study showed the endocytosis of microperoxidase to be strongly dependent on protein kinase C, protein phosphatase, extracellular signal-related kinase, and phosphatidylinositol 3-kinase signaling networks but not on protein kinase A and mitogen-activated protein kinase signaling networks. The present study indicated that the signaling cascade regulating CF's internalization differed from the cascade for microperoxidase's endocytosis.
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. kakigi-tky@umin.ac.jp
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kakigi
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Okada
authors.forename: Taizo
authors.initials: T
authors.lastname: Takeda
authors.forename: Setsuko
authors.initials: S
authors.lastname: Takeda
authors.forename: Rie
authors.initials: R
authors.lastname: Nishioka
authors.forename: Daizo
authors.initials: D
authors.lastname: Taguchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nishimura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
mesh_terms: D000818:Animals; D004705:Endocytosis / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism*; D006168:Guinea Pigs; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D013316:Stria Vascularis / Q000166:cytology / Q000378:metabolism*
chemical_list: C010297:polycationic ferritin; D005293:Ferritins; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases