Document Detail

Tetraspanin CD37 directly mediates transduction of survival and apoptotic signals.
MedLine Citation:
PMID:  22624718     Owner:  NLM     Status:  MEDLINE    
Tetraspanins are commonly believed to act only as "molecular facilitators," with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, whereas the second lies in a predicted "ITAM motif" in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.
Rosa Lapalombella; Yuh-Ying Yeh; Liwen Wang; Asha Ramanunni; Sarwish Rafiq; Shruti Jha; Justin Staubli; David M Lucas; Rajeswaran Mani; Sarah E M Herman; Amy J Johnson; Arletta Lozanski; Leslie Andritsos; Jeffrey Jones; Joseph M Flynn; Brian Lannutti; Peter Thompson; Paul Algate; Scott Stromatt; David Jarjoura; Xiaokui Mo; Dasheng Wang; Ching-Shih Chen; Gerard Lozanski; Nyla A Heerema; Susheela Tridandapani; Michael A Freitas; Natarajan Muthusamy; John C Byrd
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer cell     Volume:  21     ISSN:  1878-3686     ISO Abbreviation:  Cancer Cell     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-25     Completed Date:  2012-07-26     Revised Date:  2013-06-24    
Medline Journal Info:
Nlm Unique ID:  101130617     Medline TA:  Cancer Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  694-708     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
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MeSH Terms
Amino Acid Motifs
Amino Acid Sequence
Antigens, Neoplasm / chemistry,  genetics,  metabolism*
Apoptosis* / drug effects
Apoptosis Regulatory Proteins / genetics,  metabolism
B-Lymphocytes / drug effects,  metabolism*,  pathology
Cell Line, Tumor
Cell Survival
Chromatography, Liquid
Forkhead Transcription Factors / metabolism
HEK293 Cells
Immunoglobulin G / pharmacology
Leukemia, Lymphocytic, Chronic, B-Cell / genetics,  metabolism*,  pathology
Membrane Microdomains / metabolism
Membrane Potential, Mitochondrial
Membrane Proteins / genetics,  metabolism
Molecular Sequence Data
Phosphatidylinositol 3-Kinase / metabolism
Protein Transport
Proteomics / methods
Proto-Oncogene Proteins / genetics,  metabolism
RNA Interference
Recombinant Fusion Proteins / pharmacology
Signal Transduction* / drug effects
Tandem Mass Spectrometry
Tetraspanins / chemistry,  genetics,  metabolism*
Time Factors
Grant Support
1K12 CA133250/CA/NCI NIH HHS; K12 CA133250/CA/NCI NIH HHS; P01 CA095426/CA/NCI NIH HHS; P01 CA101956/CA/NCI NIH HHS; P01 CA81534/CA/NCI NIH HHS; P01 CA95426/CA/NCI NIH HHS; P30 CA016058/CA/NCI NIH HHS; P50 CA140158/CA/NCI NIH HHS; P50 CA140158/CA/NCI NIH HHS; R01 CA107106/CA/NCI NIH HHS; R01 CA107106/CA/NCI NIH HHS; R01 CA159296/CA/NCI NIH HHS
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/CD37 protein, human; 0/FOXO3 protein, human; 0/Forkhead Transcription Factors; 0/Immunoglobulin G; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/Recombinant Fusion Proteins; 0/TRU 016; 0/Tetraspanins; 55520-40-6/Tyrosine; EC 3-Kinase
Comment In:
Cancer Cell. 2012 May 15;21(5):597-8   [PMID:  22624709 ]

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