CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Miki, H.
Right arrow Articles by Takenawa, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miki, H.
Right arrow Articles by Takenawa, T.

Cell Growth & Differentiation, Vol 8, Issue 2 195-202, Copyright © 1997 by American Association of Cancer Research


ARTICLES

Tyrosine kinase signaling regulates Wiskott-Aldrich syndrome protein function, which is essential for megakaryocyte differentiation

H Miki, S Nonoyama, Q Zhu, A Aruffo, HD Ochs and T Takenawa
Department of Biochemistry, University of Tokyo, Japan.

Platelets are produced from megakaryocytes differentiated from megakaryoblasts, but the differentiation mechanism still remains unknown. Here, we demonstrate that a tyrosine kinase signaling regulates Wiskott-Aldrich syndrome protein (WASP), which is essential for megakaryocyte differentiation. MEG-01 megakaryoblastic cells differentiate into large multinucleated megakaryocyte-like cells characterized by microvesicle formation with a protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol 13-acetate. With parallel to the differentiation, WASP begins to accumulate at microvesicles with actin filaments and associates with tyrosine-phosphorylated Shc, the phosphorylation of which is induced. Moreover, a tyrosine kinase inhibitor, herbimycin A, blocked not only phosphorylation of Shc but also microvesicle formation without affecting cell enlargement and multinucleation, whereas a PKC inhibitor, H-7, completely inhibited all these processes. Because WASP also binds to Ash/Grb2 SH3 domains and the association of Ash/Grb2 and Shc is induced by 12-O-tetradecanoylphorbol 13-acetate treatment, a signaling pathway, PKC-tyrosine kinase-Shc-Ash/Grb2-WASP, is suggested for regulating megakaryocyte differentiation. In addition, WASP antisense oligonucleotide treatment abolishes both microvesicle formation and gathering of actin filaments. These data clearly show that WASP controls the assembly of actin filaments required for microvesicle formation downstream of PKC-tyrosine kinase.


This article has been cited by other articles:


Home page
BloodHome page
M. Mani, S. Venkatasubrahmanyam, M. Sanyal, S. Levy, A. Butte, K. Weinberg, and T. Jahn
Wiskott-Aldrich syndrome protein is an effector of Kit signaling
Blood, October 1, 2009; 114(14): 2900 - 2908.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
J. Withee, B. Galligan, N. Hawkins, and G. Garriga
Caenorhabditis elegans WASP and Ena/VASP Proteins Play Compensatory Roles in Morphogenesis and Neuronal Cell Migration
Genetics, July 1, 2004; 167(3): 1165 - 1176.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
P. Rojnuckarin and K. Kaushansky
Actin reorganization and proplatelet formation in murine megakaryocytes: the role of protein kinase C{alpha}
Blood, January 1, 2001; 97(1): 154 - 161.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
W. H. Raskind, K. K. Niakan, J. Wolff, M. Matsushita, T. Vaughan, G. Stamatoyannopoulos, C. Watanabe, J. Rios, and H. D. Ochs
Mapping of a syndrome of X-linked thrombocytopenia with thalassemia to band Xp11-12: further evidence of genetic heterogeneity of X-linked thrombocytopenia
Blood, April 1, 2000; 95(7): 2262 - 2268.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
B. S. Gross, J. I. Wilde, L. Quek, H. Chapel, D. L. Nelson, and S. P. Watson
Regulation and Function of WASp in Platelets by the Collagen Receptor, Glycoprotein VI
Blood, December 15, 1999; 94(12): 4166 - 4176.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
A. Shcherbina, F. S. Rosen, and E. Remold-O'Donnell
WASP Levels in Platelets and Lymphocytes of Wiskott-Aldrich Syndrome Patients Correlate with Cell Dysfunction
J. Immunol., December 1, 1999; 163(11): 6314 - 6320.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
J. Zhang, A. Shehabeldin, L. A.G. da Cruz, J. Butler, A.-K. Somani, M. McGavin, I. Kozieradzki, A. O. dos Santos, A. Nagy, S. Grinstein, et al.
Antigen Receptor-Induced Activation and Cytoskeletal Rearrangement Are Impaired in Wiskott-Aldrich Syndrome Protein-Deficient Lymphocytes
J. Exp. Med., November 1, 1999; 190(9): 1329 - 1342.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. Kato, H. Miki, K. Imai, S. Nonoyama, T. Suzuki, C. Sasakawa, and T. Takenawa
Wiskott-Aldrich Syndrome Protein Induces Actin Clustering without Direct Binding to Cdc42
J. Biol. Chem., September 17, 1999; 274(38): 27225 - 27230.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
E. Haddad, E. Cramer, C. Riviere, P. Rameau, F. Louache, J. Guichard, D. L. Nelson, A. Fischer, W. Vainchenker, and N. Debili
The Thrombocytopenia of Wiskott Aldrich Syndrome Is Not Related to a Defect in Proplatelet Formation
Blood, July 15, 1999; 94(2): 509 - 518.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
C. K. Miranti, S. Ohno, and J. S. Brugge
Protein Kinase C Regulates Integrin-induced Activation of the Extracellular Regulated Kinase Pathway Upstream of Shc
J. Biol. Chem., April 9, 1999; 274(15): 10571 - 10581.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
Y. Baba, S. Nonoyama, M. Matsushita, T. Yamadori, S. Hashimoto, K. Imai, S. Arai, T. Kunikata, M. Kurimoto, T. Kurosaki, et al.
Involvement of Wiskott-Aldrich Syndrome Protein in B-Cell Cytoplasmic Tyrosine Kinase Pathway
Blood, March 15, 1999; 93(6): 2003 - 2012.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
T. Nakamura, S. Muraoka, R. Sanokawa, and N. Mori
N-Shc and Sck, Two Neuronally Expressed Shc Adapter Homologs: THEIR DIFFERENTIAL REGIONAL EXPRESSION IN THE BRAIN AND ROLES IN NEUROTROPHIN AND Src SIGNALING
J. Biol. Chem., March 20, 1998; 273(12): 6960 - 6967.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Y. Wu, S. D. Spencer, and L. A. Lasky
Tyrosine Phosphorylation Regulates the SH3-mediated Binding of the Wiskott-Aldrich Syndrome Protein to PSTPIP, a Cytoskeletal-associated Protein
J. Biol. Chem., March 6, 1998; 273(10): 5765 - 5770.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1997 by the American Association of Cancer Research.