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09 28, 2020;9 (10):

Role of Vitamin K-Dependent Factors Protein S and GAS6 and TAM Receptors in SARS-CoV-2 Infection and COVID-19-Associated Immunothrombosis.

Anna Tutusaus, Montserrat Marí, José T Ortiz-Pérez, Gerry A F Nicolaes, Albert Morales, Pablo García de Frutos
Author Information
  1. Anna Tutusaus: Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain. ORCID
  2. Montserrat Marí: Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain. ORCID
  3. José T Ortiz-Pérez: Clinic Cardiovascular Institute, Hospital Clinic Barcelona, 08036 Barcelona, Spain. ORCID
  4. Gerry A F Nicolaes: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
  5. Albert Morales: Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain. ORCID
  6. Pablo García de Frutos: Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain. ORCID
PMID: 32998369 DOI: 10.3390/cells9102186

Abstract

The Vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 Infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the Immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.

Keywords

AXL GAS6 MERTK coagulation endothelium immune response viral infection

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Grants

  1. RTI2018-095672-B-I00/Ministerio de Ciencia, Innovación y Universidades
  2. PI19/01410/INSTITUTO DE SALUD CARLOS III
  3. PI15/00531/INSTITUTO DE SALUD CARLOS III

MeSH Term

Adaptive Immunity
Animals
COVID-19
Coronavirus Infections
Hemostasis
Humans
Intercellular Signaling Peptides and Proteins
Pandemics
Pneumonia, Viral
Protein S
Thrombosis
c-Mer Tyrosine Kinase

Chemicals

Intercellular Signaling Peptides and Proteins
PROS1 protein, human
Protein S
growth arrest-specific protein 6
c-Mer Tyrosine Kinase
Journal Article Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 5

Word Cloud

Created with Highcharts 10.0.0TAMGAS6systemSARS-CoV-2COVID-19viralStyrosineAXLMERTKvascularresponsesignalingimmuneinvolvedimportantroleinfectionpathologyvitaminK-dependentfactorsproteinPROS1growth-arrest-specificgene6kinasereceptorsTYRO3subfamilyreceptorkinasesRTKkeyregulatorsinflammationdamagelargelystudiedcancercoagulation-relatedpathologiesestablishedbiologicalfunctionsGAS6-PROS1/TAMpostulatedplayprogressioncomplicationsparticipationfunctionpreviouslyreportedHowevercontextTAMsprovidenewcluesvirus-hostinterplayconsequenceswayunderstandmimicryusedinfectcellsimmunothrombosisassociatedrespiratoryfailurepatientsseemsdifferentstagesdiseasetargetingbecominginterestingbiomedicalstrategyusefultreatmentnowalsoinflammatorydiseasesfutureRoleVitaminK-DependentFactorsProteinReceptorsInfectionCOVID-19-AssociatedImmunothrombosiscoagulationendothelium

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