PMID- 23602387
OWN - NLM
STAT- MEDLINE
DCOM- 20130627
LR  - 20211021
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Print)
IS  - 1534-5807 (Linking)
VI  - 25
IP  - 2
DP  - 2013 Apr 29
TI  - Endosomal type Igamma PIP 5-kinase controls EGF receptor lysosomal sorting.
PG  - 144-55
LID - S1534-5807(13)00159-7 [pii]
LID - 10.1016/j.devcel.2013.03.010 [doi]
AB  - Endosomal trafficking and degradation of epidermal growth factor receptor (EGFR) 
      play an essential role in the control of its signaling. 
      Phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P(2)) is an established regulator 
      of endocytosis, whereas PtdIns3P modulates endosomal trafficking. However, we 
      demonstrate here that type I gamma phosphatidylinositol phosphate 5-kinase i5 
      (PIPKIgammai5), an enzyme that synthesizes PtdIns4,5P(2), controls 
      endosome-to-lysosome sorting of EGFR. In this pathway, PIPKIgammai5 interacts with 
      sorting nexin 5 (SNX5), a protein that binds PtdIns4,5P(2) and other 
      phosphoinositides. PIPKIgammai5 and SNX5 localize to endosomes, and loss of either 
      protein blocks EGFR sorting into intraluminal vesicles (ILVs) of the 
      multivesicular body. Loss of ILV sorting greatly enhances and prolongs EGFR 
      signaling. PIPKIgammai5 and SNX5 prevent Hrs ubiquitination, and this facilitates the 
      Hrs association with EGFR that is required for ILV sorting. These findings reveal 
      that PIPKIgammai5 and SNX5 form a signaling nexus that controls EGFR endosomal 
      sorting, degradation, and signaling.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Sun, Yue
AU  - Sun Y
AD  - University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI 
      53706, USA.
FAU - Hedman, Andrew C
AU  - Hedman AC
FAU - Tan, Xiaojun
AU  - Tan X
FAU - Schill, Nicholas J
AU  - Schill NJ
FAU - Anderson, Richard A
AU  - Anderson RA
LA  - eng
GR  - CA104708/CA/NCI NIH HHS/United States
GR  - T32 GM008688/GM/NIGMS NIH HHS/United States
GR  - T32 GMGM08688/PHS HHS/United States
GR  - R01 CA104708/CA/NCI NIH HHS/United States
GR  - P30 CA014520/CA/NCI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - R01 GM057549/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130418
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SNX5 protein, human)
RN  - 0 (Sorting Nexins)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amino Acid Sequence
MH  - Blotting, Western
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Endocytosis/physiology
MH  - Endosomes/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - ErbB Receptors/genetics/*metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Immunoprecipitation
MH  - Lysosomes/*metabolism
MH  - Molecular Sequence Data
MH  - Phosphatidylinositol 4,5-Diphosphate/*metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Protein Binding
MH  - Protein Transport
MH  - Proteolysis
MH  - RNA, Small Interfering/genetics
MH  - Signal Transduction
MH  - Sorting Nexins/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - Two-Hybrid System Techniques
MH  - Ubiquitination
PMC - PMC3740164
MID - NIHMS459779
COIS- The authors declare no competing financial interests.
EDAT- 2013/04/23 06:00
MHDA- 2013/06/29 06:00
PMCR- 2014/04/29
CRDT- 2013/04/23 06:00
PHST- 2012/07/29 00:00 [received]
PHST- 2013/01/24 00:00 [revised]
PHST- 2013/03/15 00:00 [accepted]
PHST- 2013/04/23 06:00 [entrez]
PHST- 2013/04/23 06:00 [pubmed]
PHST- 2013/06/29 06:00 [medline]
PHST- 2014/04/29 00:00 [pmc-release]
AID - S1534-5807(13)00159-7 [pii]
AID - 10.1016/j.devcel.2013.03.010 [doi]
PST - ppublish
SO  - Dev Cell. 2013 Apr 29;25(2):144-55. doi: 10.1016/j.devcel.2013.03.010. Epub 2013 
      Apr 18.