Training
- B.S., Biology, 1953, University of Dubuque, Dubuque, Iowa
- M.S., Chemistry, 1956, New York University
- Ph.D., Biochemistry, 1960, Cornell University Medical College
Appointments
- Instructor, Pharmacology, Cornell University Medical College, 1963-1964
- Assistant Professor of Pharmacology, Cornell University Medical College,
1964-1967
- Associate Professor of Pharmacology, Cornell University Medical College,
1967-1973
- Acting Chairman, Pharmacology, Cornell University Medical College, 1971-1972
- Professor of Pharmacology, Cornell University Medical College, 1973-1975
- Professor of Physiology and Biophysics, Graduate School of Medical
Sciences, Cornell University Medical College, 1973-1975
- Professor and Chairman of Pharmacology and Therapeutics, Medical
University of Ohio, 1975-1997
- Professor of Pharmacology and Therapeutics, 1997-2005
- Professor and Chairman, Department of Physiology and Pharmacology, University
of Toledo College of Medicine, Health Science Campus, 2006-
Research Interests:
Structure and function of the digitalis
receptor.
The laboratory has had a long-standing interest in the mechanism of ion
transport across biological membranes, with a major emphasis on the properties
and functions of (Na+,K+)-ATPase (the sodium pump) of the eucaryotic plasma
membrane.
Current work of the laboratory is primarily on the interactions of (Na+,K+)-ATPase
with non-ATPase proteins, leading to the newly discovered functions of (Na+,K+)-ATPase
as a signal transducer that regulates growth of the cardiac myocyte.
Representative Publications
- Sarvazyan,
N.A., Modyanov, N.N., and Askari, A. (1995): Intersubunit and intrasubunit
contact regions of Na+/K+-ATPase revealed by controlled proteolysis and
chemical cross-linking. J. Biol. Chem. 270:26528-26532.
- Xie,
Z., Wang, Y., Liu, G., Zolotarjova, N., Periyasamy, S.M., and Askari, A.
(1996): Similarities and differences between the properties of native and
recombinant Na+/K+-ATPases. Arch. Biochem. Biophys. 330:153-162.
- Liu,
G., Xie, Z., Modyanov, N.N., and Askari, A. (1996): Restoration of phosphorylation
capacity to the dormant half of the alpha-subunits of Na+,K+- ATPase. FEBS
Lett. 390:323-326.
- Sarvazyan,
N.A., Ivanov, A., Modyanov, N.N., and Askari, A. (1997): Ligand-sensitive
interactions among the transmembrane helices of Na+/K+- ATPase. J. Biol.
Chem. 272:7855-7858.
- Liu,
L. and Askari, A. (1997): Evidence for the existence of two ATP- sensitive
Rb+ occlusion pockets within the transmembrane domains of Na+/K+- ATPase.
J. Biol. Chem. 272:14380-14386.
- Ivanov,
A., Askari, A., and Modyanov, N.N. (1997): Structural analysis of the
products of chymotryptic cleavage of the E1 form of Na,K-ATPase alpha- subunit:
identification of the N-terminal fragments containing the transmembrane
H1-H2 domain. FEBS Lett. 420:107-111.
- Kometiani,
P., Li, J., Gnudi, L., Kahn, B.B., Askari, A., and Xie, Z. (1998): Multiple
signal transduction pathways link Na+/K+-ATPase to growth- related genes
in cardiac myocytes. J. Biol. Chem. 273:15249-15256.
- Xie,
Z., Kometiani, P., Liu, J., Li, J., Shapiro, J.I., and Askari, A. (1999):
Intracellular reactive oxygen species mediate the linkage of Na+/K+- ATPase
to hypertrophy and its marker genes in cardiac myocytes. J. Biol. Chem.
274:19323-19328.
- Haas,
M., Askari, A., and Xie, Z. (2000) Involvement of Src and epidermal
growth factor receptor in the signal transducing function of Na+/K+-ATPase.
J. Biol. Chem. 275:27832-27837.
- Liu,
J., Tian, J., Haas, M., Shapiro, J.I., Askari, A., and Xie, Z. (2000)
Ouabain interaction with cardiac Na+/K+-ATPase initiates signal cascades
independent of changes in intracellular Na+ and Ca2+ concentrations. J.
Biol. Chem. 275:27838-27844.
- Askari, A. (2000) Significance of Protein-Protein Interactions to Na+/K+-ATPase
Functions. in Na/K-ATPase and Related ATPase, K. Taniguchi and S. Kaya,
Eds., pp. 17-26, Excerpta Medica Internat. Congress Series 1207, Elsevier,
Amsterdam.
- Kometiani,
P., Askari, A., Liu, J., Xie, Z., and Askari, F.K. (2000) Downregulation
of cardiac myocyte Na+/K+-ATPase by adenovirus-mediated expression of an
alpha-subunit fragment. Am. J. Physiol. 280:H415-H421.
- Mohammadi,
K., Kometiani, P., Xie, Z., and Askari, A. (2001) Role of protein kinase
C in the signal pathways that link Na+/K+-ATPase to ERK1/2. J. Biol. Chem.
276:42050-42056.
- Xie,
Z. and Askari, Z. (2002) Na+/K+-ATPase as a signal transducer. Eur.
J. Biochem. 269:2434-2439.
- Ivanov,
A.V., Modyanov, N.N., and Askari, A. (2002) Role of the self-association
of beta-subunits in the oligomeric structure of Na+/K+-ATPase. Biochem.
J. 364:293-299.
- Mohammadi,
K., Liu, L., Tian, J., Kometiani, P., Xie, Z., and Askari, A. (2003)
The positive inotropic effects of ouabain on the isolated heart is accompanied
by the activation of signal pathways that link Na/K-ATPase to ERK1/2. J.
Cardiovasc. Pharmacol. 41:609-614.
- Liu,
L., Mohammadi, K., Aynafshar B., Wang, H., Li D., Liu J., Ivanov, AV., Xie,
Z., and Askari, A. (2003) Role of caveolae in the signal transducing
function of cardiac Na+/K+-ATPase. Am. J. Physiol. 284:C1550-C1560.
- Liu,
L., Abramowitz, J., Askari, A., and Allen, J. (2004) Role of caveolae
in ouabain-induced proliferation of cultured vascular smooth muscle cells
of the synthetic phenotype. Am. J. Physiol. Heart Circ. Physiol. 287: H2173-H2182.
- Kometiani,
P.K., Liu, L., and Askari, A. (2005) Digitalis-induced signaling by
Na+/K+-ATPase in human breast cancer cells. Mol. Pharmacol. 67:929-936.
- Liu,
L. and Askari, A. (2006) The beta-subunit of cardiac Na+/K+-ATPase dictates
the concentration of the functional enzyme in caveolae. Am
J Physiol Cell Physiol. 291: C569-C578.
- Liu,
L. and Askari, A. (2006) On the importance and mechanism of amplification
of digitalis signal through Na+/K+-ATPase. Cell Mol Biol (Noisy-le-grand). 52(8):28-30.
- Liu,
L., Gable, M.E., Garlid, K.D., and Askari, A. (2007) Interactions
of K(+) (ATP) channel blockers with Na (+)/K (+)-ATPase. Mol Cell
Biochem. 306(1-2):231-237.
- Liu,
L., Zhao, X., Pierre, S.V., and Askari, A. (2007) Association
of PI3K-Akt signaling pathway with digitalis-induced hypertrophy of cardiac
myocytes. Am J Physiol Cell Physiol. 293(5):C1489-497.
- Morrill,
G.A., Kostellow, A.B., and Askari, A. Progesterone binding to
the alpha1-subunit of the Na/K-ATPase on the cell surface: insights from
computational modeling. Steroids. 2008 Jan; 73(1):27-40.
