Proteomic and phospho-proteomic profile of human platelets in basal, resting state

Insights into integrin signaling

Amir H. Qureshi, Vineet Chaoji, Dony Maiguel, Mohd Hafeez Faridi, Constantinos J. Barth, Saeed M. Salem, Mudita Singhal, Darren Stoub, Bryan Krastins, Mitsunori Ogihara, Mohammed J. Zaki, Vineet Gupta

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin αIIbβ3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin αIIbβ3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin αIIbβ3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future.

Original languageEnglish
Article numbere7627
JournalPLoS One
Volume4
Issue number10
DOIs
Publication statusPublished - 27 Oct 2009
Externally publishedYes

Fingerprint

integrins
Platelets
Integrins
Proteomics
proteomics
protein-protein interactions
Blood Platelets
Proteins
phosphorylation
Protein Interaction Maps
atherogenesis
Phosphorylation
thrombin
epinephrine
proteome
blood vessels
protein kinases
signal transduction
tail
proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Qureshi, A. H., Chaoji, V., Maiguel, D., Faridi, M. H., Barth, C. J., Salem, S. M., ... Gupta, V. (2009). Proteomic and phospho-proteomic profile of human platelets in basal, resting state: Insights into integrin signaling. PLoS One, 4(10), [e7627]. https://doi.org/10.1371/journal.pone.0007627

Proteomic and phospho-proteomic profile of human platelets in basal, resting state : Insights into integrin signaling. / Qureshi, Amir H.; Chaoji, Vineet; Maiguel, Dony; Faridi, Mohd Hafeez; Barth, Constantinos J.; Salem, Saeed M.; Singhal, Mudita; Stoub, Darren; Krastins, Bryan; Ogihara, Mitsunori; Zaki, Mohammed J.; Gupta, Vineet.

In: PLoS One, Vol. 4, No. 10, e7627, 27.10.2009.

Research output: Contribution to journalArticle

Qureshi, AH, Chaoji, V, Maiguel, D, Faridi, MH, Barth, CJ, Salem, SM, Singhal, M, Stoub, D, Krastins, B, Ogihara, M, Zaki, MJ & Gupta, V 2009, 'Proteomic and phospho-proteomic profile of human platelets in basal, resting state: Insights into integrin signaling', PLoS One, vol. 4, no. 10, e7627. https://doi.org/10.1371/journal.pone.0007627
Qureshi, Amir H. ; Chaoji, Vineet ; Maiguel, Dony ; Faridi, Mohd Hafeez ; Barth, Constantinos J. ; Salem, Saeed M. ; Singhal, Mudita ; Stoub, Darren ; Krastins, Bryan ; Ogihara, Mitsunori ; Zaki, Mohammed J. ; Gupta, Vineet. / Proteomic and phospho-proteomic profile of human platelets in basal, resting state : Insights into integrin signaling. In: PLoS One. 2009 ; Vol. 4, No. 10.
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