Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling.
During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin alphaIIbbeta3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to ac...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-10-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2762604?pdf=render |
| _version_ | 1819327108183228416 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Amir H Qureshi |
| collection | DOAJ |
| description | During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin alphaIIbbeta3 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 alphaIIbbeta3 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 alphaIIbbeta3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future. |
| first_indexed | 2024-12-24T13:05:36Z |
| format | Article |
| id | doaj.art-662aa7611cca4803aa05925336fc84ff |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T13:05:36Z |
| publishDate | 2009-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-662aa7611cca4803aa05925336fc84ff2022-12-21T16:54:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e762710.1371/journal.pone.0007627Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling.Amir H QureshiVineet ChaojiDony MaiguelMohd Hafeez FaridiConstantinos J BarthSaeed M SalemMudita SinghalDarren StoubBryan KrastinsMitsunori OgiharaMohammed J ZakiVineet GuptaDuring atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin alphaIIbbeta3 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 alphaIIbbeta3 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 alphaIIbbeta3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future.http://europepmc.org/articles/PMC2762604?pdf=render |
| spellingShingle | 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 Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling. PLoS ONE |
| title | Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling. |
| title_full | Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling. |
| title_fullStr | Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling. |
| title_full_unstemmed | Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling. |
| title_short | Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling. |
| title_sort | proteomic and phospho proteomic profile of human platelets in basal resting state insights into integrin signaling |
| url | http://europepmc.org/articles/PMC2762604?pdf=render |
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