PMID- 27974454
OWN - NLM
STAT- MEDLINE
DCOM- 20170815
LR  - 20180124
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 198
IP  - 2
DP  - 2017 Jan 15
TI  - The Systemic Lupus Erythematosus-Associated Single Nucleotide Polymorphism 
      rs1143678 in Integrin alphaM Cytoplasmic Tail Generates a 14-3-3zeta Binding Site That 
      Is Proinflammatory.
PG  - 883-894
LID - 10.4049/jimmunol.1601447 [doi]
AB  - The leukocyte integrin alpha(M)beta(2) (CR3 or Mac-1) has both proinflammatory and 
      immune regulatory functions. Genome-wide association studies have identified 
      several ITGAM (alpha(M) subunit) single nucleotide polymorphisms that are associated 
      with systemic lupus erythematosus. The single nucleotide polymorphism rs1143678 
      substitutes Pro(1146) for Ser in the integrin alpha(M) cytoplasmic tail. A detailed 
      functional characterization of this substitution is lacking. Using transfected 
      human cell lines, reconstituted mouse bone marrow neutrophils, and bone 
      marrow-derived macrophages (BMDMs), we showed that P1146S (PS) substitution 
      promoted integrin alpha(M)beta(2)-mediated adhesion, spreading, and migration of cells 
      on iC3b and fibrinogen. In the presence of LPS together with iC3b or fibrinogen, 
      the expression levels of IL-6 and TNF-alpha in integrin alpha(M(PS))beta(2) BMDMs were 
      significantly higher than those of integrin alpha(M(wild-type))beta(2) BMDMs, and they 
      showed faster kinetics of Erk1/2 activation through the src family kinase(s)-Syk 
      signaling pathway. Integrin alpha(M(PS))beta(2) BMDMs also exhibited higher levels of 
      active RhoA and phagocytic activity. Mechanistically, P1146S substitution in the 
      alpha(M) cytoplasmic tail generates a noncanonical 14-3-3zeta binding site that 
      modulates integrin alpha(M(PS))beta(2) outside-in signaling.
CI  - Copyright (c) 2017 by The American Association of Immunologists, Inc.
FAU - Ong, Li-Teng
AU  - Ong LT
AUID- ORCID: 0000-0001-6741-6009
AD  - School of Biological Sciences, Nanyang Technological University, Singapore 
      637551, Singapore.
FAU - Tan, Hui-Foon
AU  - Tan HF
AD  - School of Biological Sciences, Nanyang Technological University, Singapore 
      637551, Singapore.
FAU - Feng, Chen
AU  - Feng C
AD  - School of Biological Sciences, Nanyang Technological University, Singapore 
      637551, Singapore.
FAU - Qu, Jing
AU  - Qu J
AD  - School of Biological Sciences, Nanyang Technological University, Singapore 
      637551, Singapore.
FAU - Loh, Shuzk-Cheng
AU  - Loh SC
AD  - School of Biological Sciences, Nanyang Technological University, Singapore 
      637551, Singapore.
FAU - Bhattacharyya, Surajit
AU  - Bhattacharyya S
AD  - School of Biological Sciences, Nanyang Technological University, Singapore 
      637551, Singapore.
FAU - Tan, Suet-Mien
AU  - Tan SM
AD  - School of Biological Sciences, Nanyang Technological University, Singapore 
      637551, Singapore smtan@ntu.edu.sg.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161214
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Macrophage-1 Antigen)
SB  - IM
MH  - 14-3-3 Proteins/*metabolism
MH  - Animals
MH  - Binding Sites
MH  - Flow Cytometry
MH  - Fluorescence Resonance Energy Transfer
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Lupus Erythematosus, Systemic/*genetics/metabolism
MH  - Macrophage-1 Antigen/*genetics
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide
EDAT- 2016/12/16 06:00
MHDA- 2017/08/16 06:00
CRDT- 2016/12/16 06:00
PHST- 2016/08/19 00:00 [received]
PHST- 2016/11/16 00:00 [accepted]
PHST- 2016/12/16 06:00 [pubmed]
PHST- 2017/08/16 06:00 [medline]
PHST- 2016/12/16 06:00 [entrez]
AID - jimmunol.1601447 [pii]
AID - 10.4049/jimmunol.1601447 [doi]
PST - ppublish
SO  - J Immunol. 2017 Jan 15;198(2):883-894. doi: 10.4049/jimmunol.1601447. Epub 2016 
      Dec 14.