|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 April 2002, Vol. 99, No. 7, pp. 2418-2426
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Adducin in platelets: activation-induced phosphorylation by
PKC and proteolysis by calpain
Diana M. Gilligan,
Rami Sarid, and
Joleen Weese
From the Department of Internal Medicine (Hematology),
Yale University School of Medicine, New Haven, CT; and the Puget Sound
Blood Center and the Department of Medicine (Hematology), University of
Washington School of Medicine, Seattle.
Adducins are a family of cytoskeletal proteins encoded by 3 genes
(alpha, beta, and gamma). Platelets express alpha and gamma adducins,
in contrast to red blood cells that express alpha and beta adducins.
During platelet activation with thrombin, calcium ionophore A23187, or
phorbol 12-myristate 13-acetate, alpha and gamma adducins were
phosphorylated by protein kinase C (PKC) as detected by an antibody
specific for a phosphopeptide sequence in the highly conserved carboxy
terminus. Platelet activation also led to adducin proteolysis;
inhibition by calpeptin suggests that the protease was calpain. The
kinase inhibitor staurosporine inhibited PKC phosphorylation of adducin
and also inhibited proteolysis of adducin. Experiments with recombinant
alpha adducin demonstrated that the PKC-phosphorylated form was
proteolyzed at a significantly faster rate than the unphosphorylated
form. The concentration of adducin in platelets was estimated at 6 µM, similar to the concentration of capping protein. Fractionation of
platelets into high-speed supernatant (cytosol) and pellet (membrane
and cytoskeleton) revealed a shift of PKC-phosphorylated adducin to the
cytosol during platelet activation. Platelet aggregation detected
turbidometrically was decreased in the presence of staurosporine and
was completely inhibited by calpeptin. Thrombin-induced changes in
morphology were assessed by confocal microscopy with fluorescein
phalloidin and were not prevented by staurosporine or calpeptin. Our
results suggest that regulation of adducin function by PKC and calpain may play a role in platelet aggregation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C.-L. Chen, Y.-T. Hsieh, and H.-C. Chen
Phosphorylation of adducin by protein kinase C{delta} promotes cell motility
J. Cell Sci.,
April 1, 2007;
120(7):
1157 - 1167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Pula, K. Schuh, K. Nakayama, K. I. Nakayama, U. Walter, and A. W. Poole
PKC{delta} regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation
Blood,
December 15, 2006;
108(13):
4035 - 4044.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Kalfa, S. Pushkaran, N. Mohandas, J. H. Hartwig, V. M. Fowler, J. F. Johnson, C. H. Joiner, D. A. Williams, and Y. Zheng
Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton
Blood,
December 1, 2006;
108(12):
3637 - 3645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Rabenstein, N. A. Addy, B. J. Caldarone, Y. Asaka, L. M. Gruenbaum, L. L. Peters, D. M. Gilligan, R. M. Fitzsimonds, and M. R. Picciotto
Impaired Synaptic Plasticity and Learning in Mice Lacking {beta}-Adducin, an Actin-Regulating Protein
J. Neurosci.,
February 23, 2005;
25(8):
2138 - 2145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Lahortiga, J. L. Vizmanos, X. Agirre, I. Vazquez, J. C. Cigudosa, M. J. Larrayoz, F. Sala, A. Gorosquieta, K. Perez-Equiza, M. J. Calasanz, et al.
NUP98 Is Fused to Adducin 3 in a Patient with T-Cell Acute Lymphoblastic Leukemia and Myeloid Markers, with a New Translocation t(10;11)(q25;p15)
Cancer Res.,
June 15, 2003;
63(12):
3079 - 3083.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Barkalow, J. E. Italiano Jr., D. E. Chou, Y. Matsuoka, V. Bennett, and J. H. Hartwig
{alpha}-Adducin dissociates from F-actin and spectrin during platelet activation
J. Cell Biol.,
May 12, 2003;
161(3):
557 - 570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Gruenbaum, D. M. Gilligan, M. R. Picciotto, S. Marinesco, and T. J. Carew
Identification and Characterization of Aplysia Adducin, an Aplysia Cytoskeletal Protein Homologous to Mammalian Adducins: Increased Phosphorylation at a Protein Kinase C Consensus Site during Long-Term Synaptic Facilitation
J. Neurosci.,
April 1, 2003;
23(7):
2675 - 2685.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
