Evidence map›Paper›PMID 24523237›Full record

ArticleBlood2014

ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding.

Ana Kasirer-Friede, Jian Kang, Bryan Kahner, Feng Ye, Mark H Ginsberg, Sanford J Shattil

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 67 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Ana Kasirer-FriedeHematology-Oncology Division, Department of Medicine, University of California, San Diego, La Jolla, CA.
Jian KangHematology-Oncology Division, Department of Medicine, University of California, San Diego, La Jolla, CA.
Bryan KahnerHematology-Oncology Division, Department of Medicine, University of California, San Diego, La Jolla, CA.
Feng YeHematology-Oncology Division, Department of Medicine, University of California, San Diego, La Jolla, CA.
Mark H GinsbergHematology-Oncology Division, Department of Medicine, University of California, San Diego, La Jolla, CA.
Sanford J ShattilHematology-Oncology Division, Department of Medicine, University of California, San Diego, La Jolla, CA.
University of California, San Diego · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
The Interaction of TPO and Integrins in Hematopoiesis CellsP01HL078784 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2005 to 2019
$28.3M
Discoveries at the Crossroads of Integrin and Inflammatory Signaling in PlateletsR01HL056595 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHATTIL, SANFORD J · 1996 to 2020
$7.5M
Composition and Functions of the Integrin Activation ComplexR01HL117807 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2014 to 2017
$1.5M
NCI NIH HHS P30 CA023100NHLBI NIH HHS HL56595NHLBI NIH HHS HL98208NHLBI NIH HHS P01 HL078784NHLBI NIH HHS R01 HL056595NHLBI NIH HHS R01 HL117807
6 · The paper itself

Abstract

ADAP is a hematopoietic-restricted adapter protein that promotes integrin activation and is a carrier for other adapter proteins, Src kinase-associated phosphoprotein 1 (SKAP1) and SKAP2. In T lymphocytes, SKAP1 is the ADAP-associated molecule that activates integrins through direct linkages with Rap1 effectors (regulator of cell adhesion and polarization enriched in lymphoid tissues; Rap1-interacting adapter molecule). ADAP also promotes integrin αIIbβ3 activation in platelets, which lack SKAP1, suggesting an ADAP integrin-regulatory pathway different from those in lymphocytes. Here we characterized a novel association between ADAP and 2 essential integrin-β cytoplasmic tail-binding proteins involved in αIIbβ3 activation, talin and kindlin-3. Glutathione S-transferase pull-downs identified distinct regions in ADAP necessary for association with kindlin or talin. ADAP was physically proximal to talin and kindlin-3 in human platelets, as assessed biochemically, and by immunofluorescence microscopy and proximity ligation. Relative to wild-type mouse platelets, ADAP-deficient platelets exhibited reduced co-localization of talin with αIIbβ3, and reduced irreversible fibrinogen binding in response to a protease activated receptor 4 (PAR4) thrombin receptor agonist. When ADAP was heterologously expressed in Chinese hamster ovary cells co-expressing αIIbβ3, talin, PAR1, and kindlin-3, it associated with an αIIbβ3/talin complex and enabled kindlin-3 to promote agonist-dependent ligand binding to αIIbβ3. Thus, ADAP uniquely promotes activation of and irreversible fibrinogen binding to platelet αIIbβ3 through interactions with talin and kindlin-3.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsBlood PlateletsCHO CellsCricetinaeCricetulusCytoskeletal ProteinsFibrinogenHumansMembrane ProteinsMiceNeoplasm ProteinsPlatelet Glycoprotein GPIIb-IIIa ComplexProtein BindingProtein Interaction MappingTalinAdaptor Proteins, Signal TransducingCytoskeletal ProteinsFERMT3 protein, humanFibrinogenFYB1 protein, humanFyb protein, mousekindlin-3 protein, mouseMembrane ProteinsNeoplasm ProteinsPlatelet Glycoprotein GPIIb-IIIa ComplexTalin

Identifiers

PMID24523237
PMCPMC4023421
OpenAlexW2035136679

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.