PMID- 9885253
OWN - NLM
STAT- MEDLINE
DCOM- 19990304
LR  - 20240214
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 144
IP  - 1
DP  - 1999 Jan 11
TI  - Integrin-dependent control of translation: engagement of integrin alphaIIbbeta3 
      regulates synthesis of proteins in activated human platelets.
PG  - 175-84
AB  - Integrins are widely expressed plasma membrane adhesion molecules that tether 
      cells to matrix proteins and to one another in cell-cell interactions. Integrins 
      also transmit outside-in signals that regulate functional responses of cells, and 
      are known to influence gene expression by regulating transcription. In previous 
      studies we found that platelets, which are naturally occurring anucleate 
      cytoplasts, translate preformed mRNA transcripts when they are activated by 
      outside-in signals. Using strategies that interrupt engagement of integrin 
      alphaIIbbeta3 by fibrinogen and platelets deficient in this integrin, we found 
      that alphaIIbbeta3 regulates the synthesis of B cell lymphoma 3 (Bcl-3) when 
      platelet aggregation is induced by thrombin. We also found that synthesis of 
      Bcl-3, which occurs via a specialized translation control pathway regulated by 
      mammalian target of rapamycin (mTOR), is induced when platelets adhere to 
      immobilized fibrinogen in the absence of thrombin and when integrin alphaIIbbeta3 
      is engaged by a conformation-altering antibody against integrin alphaIIbbeta3. 
      Thus, outside-in signals delivered by integrin alphaIIbbeta3 are required for 
      translation of Bcl-3 in thrombin-stimulated aggregated platelets and are 
      sufficient to induce translation of this marker protein in the absence of 
      thrombin. Engagement of integrin alpha2beta1 by collagen also triggered synthesis 
      of Bcl-3. Thus, control of translation may be a general mechanism by which 
      surface adhesion molecules regulate gene expression.
FAU - Pabla, R
AU  - Pabla R
AD  - Nora Eccles Harrison Cardiovascular Research and Training Institute, Eccles 
      Institute of Human Genetics.
FAU - Weyrich, A S
AU  - Weyrich AS
FAU - Dixon, D A
AU  - Dixon DA
FAU - Bray, P F
AU  - Bray PF
FAU - McIntyre, T M
AU  - McIntyre TM
FAU - Prescott, S M
AU  - Prescott SM
FAU - Zimmerman, G A
AU  - Zimmerman GA
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - R01 HL044525/HL/NHLBI NIH HHS/United States
GR  - R37 HL044525/HL/NHLBI NIH HHS/United States
GR  - HL44525/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (B-Cell Lymphoma 3 Protein)
RN  - 0 (BCL3 protein, human)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - B-Cell Lymphoma 3 Protein
MH  - Blood Platelets/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Extracellular Space/metabolism
MH  - Humans
MH  - Platelet Aggregation
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/immunology/*metabolism
MH  - *Protein Biosynthesis
MH  - Proto-Oncogene Proteins/*biosynthesis
MH  - Thrombin/pharmacology
MH  - Transcription Factors
PMC - PMC2148114
EDAT- 1999/01/13 00:00
MHDA- 1999/01/13 00:01
PMCR- 1999/07/11
CRDT- 1999/01/13 00:00
PHST- 1999/01/13 00:00 [pubmed]
PHST- 1999/01/13 00:01 [medline]
PHST- 1999/01/13 00:00 [entrez]
PHST- 1999/07/11 00:00 [pmc-release]
AID - 10.1083/jcb.144.1.175 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Jan 11;144(1):175-84. doi: 10.1083/jcb.144.1.175.