PMID- 20978472
OWN - NLM
STAT- MEDLINE
DCOM- 20110112
LR  - 20211020
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 29
IP  - 23
DP  - 2010 Dec 1
TI  - Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis.
PG  - 3898-910
LID - 10.1038/emboj.2010.265 [doi]
AB  - Tubby and tubby-like protein 1 (Tulp1) are newly identified phagocytosis ligands 
      to facilitate retinal pigment epithelium (RPE) and macrophage phagocytosis. Both 
      proteins without classical signal peptide have been demonstrated with 
      unconventional secretion. Here, we characterized them as novel MerTK ligands to 
      facilitate phagocytosis. Tulp1 interacts with Tyro3, Axl and MerTK of the TAM 
      receptor tyrosine kinase subfamily, whereas tubby binds only to MerTK. Excessive 
      soluble MerTK extracellular domain blocked tubby- or Tulp1-mediated phagocytosis. 
      Both ligands induced MerTK activation with receptor phosphorylation and 
      signalling cascade, including non-muscle myosin II redistribution and 
      co-localization with phagosomes. Tubby and Tulp1 are bridging molecules with 
      their N-terminal region as MerTK-binding domain and C-terminal region as 
      phagocytosis prey-binding domain (PPBD). Five minimal phagocytic determinants 
      (MPDs) of K/R(X)(1-2)KKK in Tulp1 N-terminus were defined as essential motifs for 
      MerTK binding, receptor phosphorylation and phagocytosis. PPBD was mapped to the 
      highly conserved 54 amino acids at the C-terminal end of tubby and Tulp1. These 
      data suggest that tubby and Tulp1 are novel bridging molecules to facilitate 
      phagocytosis through MerTK.
FAU - Caberoy, Nora B
AU  - Caberoy NB
AD  - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami 
      Miller School of Medicine, Miami, FL 33136, USA.
FAU - Zhou, Yixiong
AU  - Zhou Y
FAU - Li, Wei
AU  - Li W
LA  - eng
GR  - P30 EY014801/EY/NEI NIH HHS/United States
GR  - R01EY016211/EY/NEI NIH HHS/United States
GR  - P30-EY014801/EY/NEI NIH HHS/United States
GR  - R01 EY016211/EY/NEI NIH HHS/United States
GR  - R01EY016211-05S1/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101026
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Eye Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (TUB protein, human)
RN  - 0 (TULP1 protein, human)
RN  - EC 2.7.10.1 (MERTK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (c-Mer Tyrosine Kinase)
RN  - EC 3.6.1.- (Myosin Type II)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Amino Acid Motifs
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Eye Proteins/genetics/*metabolism
MH  - Humans
MH  - Macrophages/cytology
MH  - Mice
MH  - Mutation
MH  - Myosin Type II/metabolism
MH  - *Phagocytosis
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Swine
MH  - c-Mer Tyrosine Kinase
PMC - PMC3020645
COIS- The authors declare that they have no conflict of interest.
EDAT- 2010/10/28 06:00
MHDA- 2011/01/13 06:00
PMCR- 2011/12/01
CRDT- 2010/10/28 06:00
PHST- 2010/08/11 00:00 [received]
PHST- 2010/09/27 00:00 [accepted]
PHST- 2010/10/28 06:00 [entrez]
PHST- 2010/10/28 06:00 [pubmed]
PHST- 2011/01/13 06:00 [medline]
PHST- 2011/12/01 00:00 [pmc-release]
AID - emboj2010265 [pii]
AID - 10.1038/emboj.2010.265 [doi]
PST - ppublish
SO  - EMBO J. 2010 Dec 1;29(23):3898-910. doi: 10.1038/emboj.2010.265. Epub 2010 Oct 
      26.