{"id":"https://openalex.org/W2551908633","doi":"https://doi.org/10.1182/blood.v116.21.3204.3204","title":"Elevated Cytosolic Cyclic AMP Inhibits Platelet Adhesion to Von Willebrand Factor by Disengaging the Glycoprotein Ib-IX-V Complex From Lipid Rafts","display_name":"Elevated Cytosolic Cyclic AMP Inhibits Platelet Adhesion to Von Willebrand Factor by Disengaging the Glycoprotein Ib-IX-V Complex From Lipid Rafts","publication_year":2010,"publication_date":"2010-11-19","ids":{"openalex":"https://openalex.org/W2551908633","doi":"https://doi.org/10.1182/blood.v116.21.3204.3204","mag":"2551908633"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v116.21.3204.3204","doi":"https://doi.org/10.1182/blood.v116.21.3204.3204","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v116.21.3204.3204","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5050396191","display_name":"Adam D. Munday","orcid":"https://orcid.org/0000-0002-9479-6737","observed_orcids":["https://orcid.org/0000-0002-9479-6737"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]},{"id":"https://openalex.org/I2799735646","display_name":"Bloodworks Northwest","ror":"https://ror.org/00ek9j693","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I2799735646"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Adam D Munday","raw_affiliation_strings":["Puget Sound Blood Center, University of Washingtom, Seattle, WA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Puget Sound Blood Center, University of Washingtom, Seattle, WA, USA,","institution_ids":["https://openalex.org/I201448701","https://openalex.org/I2799735646"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5071086626","display_name":"Rebecca A. Penkala","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Rebecca A Penkala","raw_affiliation_strings":["Bioengineering, University of Washington, Seattle, WA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bioengineering, University of Washington, Seattle, WA, USA,","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5053907304","display_name":"Pavel D Davizon","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I2799735646","display_name":"Bloodworks Northwest","ror":"https://ror.org/00ek9j693","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I2799735646"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Pavel D Davizon","raw_affiliation_strings":["Puget Sound Blood Center, Seattle, WA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Puget Sound Blood Center, Seattle, WA, USA,","institution_ids":["https://openalex.org/I2799735646"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046791205","display_name":"Clyde J Pierce","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I2799735646","display_name":"Bloodworks Northwest","ror":"https://ror.org/00ek9j693","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I2799735646"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Clyde J Pierce","raw_affiliation_strings":["Puget Sound Blood Center, Seattle, WA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Puget Sound Blood Center, Seattle, WA, USA,","institution_ids":["https://openalex.org/I2799735646"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039521339","display_name":"William E. Hobbs","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I2799735646","display_name":"Bloodworks Northwest","ror":"https://ror.org/00ek9j693","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I2799735646"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"William E Hobbs","raw_affiliation_strings":["Puget Sound Blood Center, Seattle, WA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Puget Sound Blood Center, Seattle, WA, USA,","institution_ids":["https://openalex.org/I2799735646"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044756645","display_name":"John D. Kulman","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I2799735646","display_name":"Bloodworks Northwest","ror":"https://ror.org/00ek9j693","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I2799735646"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"John D Kulman","raw_affiliation_strings":["Research Division, Puget Sound Blood Center, Seattle, WA, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Research Division, Puget Sound Blood Center, Seattle, WA, USA","institution_ids":["https://openalex.org/I2799735646"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5051799220","display_name":"Wendy E. Thomas","orcid":"https://orcid.org/0000-0001-8602-0819","observed_orcids":["https://orcid.org/0000-0001-8602-0819"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Wendy E Thomas","raw_affiliation_strings":["Bioengineering, University of Washington, Seattle, WA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Bioengineering, University of Washington, Seattle, WA, USA,","institution_ids":["https://openalex.org/I201448701"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5105003771","display_name":"Jos\u00e9 A. L\u00f3pez","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I2799735646","display_name":"Bloodworks Northwest","ror":"https://ror.org/00ek9j693","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I2799735646"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jose A. Lopez","raw_affiliation_strings":["Puget Sound Blood Center, Seattle, WA, USA,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Puget Sound Blood Center, Seattle, WA, USA,","institution_ids":["https://openalex.org/I2799735646"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5044756645","https://openalex.org/A5046791205","https://openalex.org/A5051799220","https://openalex.org/A5053907304","https://openalex.org/A5071086626"],"corresponding_institution_ids":["https://openalex.org/I201448701","https://openalex.org/I2799735646"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.33288076,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"116","issue":"21","first_page":"3204","last_page":"3204"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10746","display_name":"Platelet Disorders and Treatments","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10746","display_name":"Platelet Disorders and Treatments","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10831","display_name":"Cell Adhesion Molecules Research","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2723","display_name":"Immunology and Allergy"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/camp","display_name":"cyclic AMP","score":0.9829999804496765},{"id":"https://openalex.org/keywords/platelet-adhesion","display_name":"platelet adhesion","score":0.9660000205039978},{"id":"https://openalex.org/keywords/von-willebrand-factor","display_name":"von Willebrand factor","score":0.996999979019165},{"id":"https://openalex.org/keywords/lipid-rafts","display_name":"lipid rafts","score":0.8180000185966492},{"id":"https://openalex.org/keywords/protein-kinase-a","display_name":"protein kinase A","score":0.9480000138282776},{"id":"https://openalex.org/keywords/calmodulin","display_name":"calmodulin","score":0.7680000066757202},{"id":"https://openalex.org/keywords/14-3-3","display_name":"14-3-3\u03b6","score":0.9549999833106995},{"id":"https://openalex.org/keywords/platelet-activation","display_name":"platelet activation","score":0.47999998927116394},{"id":"https://openalex.org/keywords/prostaglandins","display_name":"prostaglandins","score":0.7509999871253967},{"id":"https://openalex.org/keywords/platelet-receptors","display_name":"platelet receptors","score":0.44999998807907104},{"id":"https://openalex.org/keywords/platelet-inhibition","display_name":"platelet aggregation inhibition","score":0.4000000059604645},{"id":"https://openalex.org/keywords/endothelium","display_name":"endothelium","score":0.3490000069141388}],"concepts":[{"id":"https://openalex.org/C2778442980","wikidata":"https://www.wikidata.org/wiki/Q17110527","display_name":"Glycoprotein Ib","level":4,"score":0.7641159296035767},{"id":"https://openalex.org/C89560881","wikidata":"https://www.wikidata.org/wiki/Q101026","display_name":"Platelet","level":2,"score":0.602766215801239},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5425321459770203},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5221726894378662},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.5062745809555054},{"id":"https://openalex.org/C2779394231","wikidata":"https://www.wikidata.org/wiki/Q412310","display_name":"Von Willebrand factor","level":3,"score":0.48963838815689087},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.48538291454315186},{"id":"https://openalex.org/C26828662","wikidata":"https://www.wikidata.org/wiki/Q7202248","display_name":"Platelet membrane glycoprotein","level":3,"score":0.4681297540664673},{"id":"https://openalex.org/C3018697912","wikidata":"https://www.wikidata.org/wiki/Q179217","display_name":"Platelet activation","level":3,"score":0.44061076641082764},{"id":"https://openalex.org/C2776057759","wikidata":"https://www.wikidata.org/wiki/Q904599","display_name":"Ristocetin","level":4,"score":0.4277363419532776},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.4156285226345062},{"id":"https://openalex.org/C2910542480","wikidata":"https://www.wikidata.org/wiki/Q2335787","display_name":"Platelet Glycoprotein GPIIb-IIIa Complex","level":4,"score":0.41143783926963806},{"id":"https://openalex.org/C108625454","wikidata":"https://www.wikidata.org/wiki/Q187126","display_name":"Glycoprotein","level":2,"score":0.4023831784725189},{"id":"https://openalex.org/C195687474","wikidata":"https://www.wikidata.org/wiki/Q409715","display_name":"Integrin","level":3,"score":0.321904718875885},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.31942814588546753},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3035394549369812},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.09231117367744446}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v116.21.3204.3204","doi":"https://doi.org/10.1182/blood.v116.21.3204.3204","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v116.21.3204.3204","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.8371999859809875,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2151645507","https://openalex.org/W2562323051","https://openalex.org/W2590122481","https://openalex.org/W2068262290","https://openalex.org/W2563900588","https://openalex.org/W2403265143","https://openalex.org/W1924175076","https://openalex.org/W7097130884","https://openalex.org/W2079695285","https://openalex.org/W2200374932"],"abstract_inverted_index":{"Abstract":[0,1],"3204":[2],"A":[3,110],"high":[4],"pressure":[5],"circulatory":[6],"system":[7],"has":[8],"two":[9,361],"diametrically":[10],"opposed":[11],"requirements":[12],"for":[13,49,116,140,464],"its":[14,290],"function:":[15],"it":[16],"must":[17],"be":[18,243],"able":[19],"to":[20,23,149,234,242,287,390,415,437,560],"rapidly":[21,54,507],"gel":[22],"prevent":[24],"blood":[25,51,64],"loss":[26],"when":[27,39,344,350,508],"the":[28,31,40,61,66,76,105,113,120,134,137,144,150,183,202,212,223,230,237,254,283,318,326,334,375,384,387,424,431,444,481,500,515,525,542,546],"integrity":[29],"of":[30,63,70,88,101,119,133,147,155,161,207,222,232,248,282,301,317,328,337,366,378,386,394,434,447,467,483,514,530,534,558],"vasculature":[32,41],"is":[33,42,46,104,127,186,289],"compromised":[34],"while":[35],"simultaneously":[36],"maintaining":[37,50],"fluidity":[38],"intact.":[43],"The":[44,98,157,197,245,504],"endothelium":[45],"primarily":[47],"responsible":[48],"fluidity,":[52],"producing":[53],"acting":[55],"labile":[56],"substances":[57,74],"that":[58,142,219,333,374,398,472],"inhibit":[59,95],"both":[60],"clotting":[62],"and":[65,68,94,170,173,182,191,275,324,413,441,451,524,551],"adhesion":[67,146,414,469],"aggregation":[69,412],"platelets.":[71],"Among":[72],"these":[73],"are":[75,175,494,510],"prostaglandins":[77],"(PGE1,":[78],"PGI2,":[79],"PGD2),":[80],"which":[81,477,539],"bind":[82,235],"platelet":[83,96,138,148,213,265,406,468],"membrane":[84],"receptors,":[85],"raise":[86],"concentrations":[87],"intracellular":[89],"cyclic":[90],"adenosine":[91],"monophosphate":[92],"(cAMP),":[93],"functions.":[97],"major":[99],"effector":[100],"increased":[102],"cAMP":[103,125,400,475,531],"serine/threonine":[106],"kinase":[107,109],"protein":[108],"(PKA).":[111],"Of":[112],"numerous":[114],"targets":[115],"PKA,":[117],"one":[118],"most":[121],"highly":[122],"phosphorylated":[123,274],"upon":[124,264],"increase":[126,399],"glycoprotein":[128],"(GP)":[129],"Ib\u03b2,":[130],"a":[131,179,194,299,381,462,518],"component":[132],"GPIb-IX-V":[135,158,360,388,435,448,484],"complex,":[136],"receptor":[139],"VWF":[141,416],"mediates":[143],"initial":[145],"vessel":[151],"wall":[152],"at":[153],"sites":[154],"injury.":[156],"complex":[159,389,516,526],"consists":[160],"4":[162],"type":[163],"I":[164],"transmembrane":[165],"polypeptides,":[166],"GPIb\u03b1,":[167],"GPIb\u03b2,":[168,535],"GPV":[169,192],"GPIX.":[171],"GPIb\u03b1":[172,208,233],"GPIb\u03b2":[174,224,249,271,338,379,501,543],"disulfide":[176],"linked":[177],"in":[178,193,259,298,383],"1:2":[180],"ratio,":[181],"resulting":[184],"GPIb":[185],"non-covalently":[187],"associated":[188,486],"with":[189,251,277,308,363,396,430,487,512],"GPIX":[190],"2:2:1":[195],"ratio.":[196],"VWF-binding":[198],"site":[199],"resides":[200],"within":[201],"N-terminal":[203,286],"300":[204],"amino":[205,257,303],"acids":[206],"500":[209],"A\u030a":[210],"above":[211],"surface.":[214],"Although":[215],"current":[216],"data":[217],"indicate":[218],"PKA":[220],"phosphorylation":[221,533],"cytoplasmic":[225,246,284,376],"domain":[226,247,377],"(at":[227],"Ser166)":[228],"inhibits":[229],"ability":[231],"VWF,":[236],"molecular":[238],"mechanism(s)":[239],"have":[240,459],"yet":[241],"elucidated.":[244],"associates":[250,276],"calmodulin":[252,262,353,367,498,522],"(in":[253],"juxtamembrane":[255],"20":[256],"acids)":[258],"resting":[260],"platelets;":[261],"dissociates":[263,523],"activation.":[266],"With":[267],"elevated":[268],"cytosolic":[269,306,474],"cAMP,":[270],"Ser166":[272,288],"becomes":[273],"14-3-3\u03b6.":[278,355],"An":[279],"interesting":[280],"feature":[281],"sequence":[285,311],"extreme":[291],"cationic":[292],"nature,":[293],"containing":[294],"8":[295],"Arg":[296],"residues":[297],"stretch":[300],"17":[302],"acids.":[304],"Other":[305],"proteins":[307],"similar":[309],"polybasic":[310,335,502],"(MARCKS,":[312],"GAP43)":[313],"function":[314,340],"as":[315,521],"organizers":[316],"signaling":[319],"phospholipid":[320],"phosphatidylinositol":[321],"4,5-bisphosphate":[322],"(PIP2),":[323],"promote":[325,532],"formation":[327],"lipid":[329,391,438,488],"rafts;":[330],"we":[331,371],"reasoned":[332],"region":[336],"might":[339],"similarly,":[341],"organizing":[342],"rafts":[343],"unbound":[345],"by":[346,352,423,449,456,470],"protein,":[347],"but":[348],"not":[349],"occupied":[351],"or":[354,402],"Platelet":[356],"activation":[357],"increases":[358],"raft-associated":[359],"fold,":[362],"concomitant":[364],"dissociation":[365],"from":[368,545],"GPIb\u03b2.":[369],"Here":[370],"present":[372],"evidence":[373],"plays":[380],"role":[382],"localization":[385,436],"rafts.":[392,489,528],"Treatment":[393],"platelets":[395,491,509],"agents":[397,471],"(PGI2":[401],"forskolin)":[403],"inhibited":[404],"GPIb-IX-V-dependent":[405],"functions,":[407],"including":[408],"ristocetin-induced":[409],"aggregation,":[410],"shear-induced":[411],"under":[417],"flow.":[418],"This":[419],"effect":[420,453],"was":[421,454],"prevented":[422],"cell-permeable":[425],"PKA-specific":[426],"inhibitor":[427],"H-89.":[428,457],"Consistent":[429],"functional":[432],"importance":[433],"rafts,":[439],"PGI2":[440],"forskolin":[442],"reduced":[443],"raft":[445,549],"content":[446],"35%,":[450],"this":[452],"reversed":[455],"We":[458],"thus":[460],"uncovered":[461],"mechanism":[463],"long-observed":[465],"inhibition":[466],"elevate":[473],"concentrations,":[476],"depends":[478],"on":[479],"modulating":[480],"quantity":[482],"complexes":[485],"\u201cResting\u201d":[490],"ex":[492],"vivo":[493],"relatively":[495],"quiescent":[496],"because":[497],"occupies":[499],"region.":[503],"situation":[505],"changes":[506],"activated,":[511],"more":[513],"assuming":[517],"ligand-competent":[519],"state":[520],"organizes":[527],"Elevations":[529],"enabling":[536],"14-3-3\u03b6":[537],"association,":[538],"also":[540],"displaces":[541],"tail":[544],"membrane,":[547],"disrupting":[548],"association":[550],"adhesive":[552],"function.":[553],"Disclosures:":[554],"No":[555],"relevant":[556],"conflicts":[557],"interest":[559],"declare.":[561]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2016-11-30T00:00:00"}
