Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation

Author:

Machlus Kellie R.12ORCID,Wu Stephen K.1,Stumpo Deborah J.3,Soussou Thomas S.1,Paul David S.4,Campbell Robert A.5,Kalwa Hermann6,Michel Thomas6,Bergmeier Wolfgang4,Weyrich Andrew S.5,Blackshear Perry J.3,Hartwig John H.1,Italiano Joseph E.127

Affiliation:

1. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Boston, MA;

2. Harvard Medical School, Boston, MA;

3. Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC;

4. Department of Biochemistry and Biophysics, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC;

5. Program in Molecular Medicine and Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT;

6. Cardiovascular Medicine Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; and

7. Vascular Biology Program, Department of Surgery, Children’s Hospital Boston, Boston, MA

Abstract

Key Points Proteomic analyses and polysome profiling of developing MKs identified a striking increase in the levels of a novel protein, MARCKS, during proplatelet formation. MARCKS deletion, inhibition, or phosphorylation inhibits proplatelet formation associated with activation of the actin-binding protein Arp2/3.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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