References:
- Efendiev, R., and Pedemonte, C.H. Contrary to the rat-type, the human-type Na,K-ATPase is phosphorylated at the same amino acid by hormones that produce opposite effects on the enzyme activity. J. Am. Soc. Nephrol., 2006, 17, 31-38
- Efendiev, R., Chen, Z., Katz, A.I., Pedemonte, C.H., and Bertorello, A.M. A 14-3-3 protein translates the Na,K-ATPase alpha-subunit phosphorylation signal into binding and activation of phosphoinositide 3-kinase during endocytosis. J. Biol. Chem., 2005, 280, 16272-16277
- Efendiev, R., Krmar, R.T., Leibiger I.B., Ogimoto, G., Zwiller, J., Tripodi, G., Katz, A., Bianchi, G., Pedemonte, C.H., and Bertorello, A.M. Hypertension-linked mutation in the adducin alpha-subunit affects AP2-mu2 phosphorylation and impairs Na+,K+-ATPase endocytosis. Circ. Res, 2004, 95, 1100-1108
- Efendiev, R., Budu, C.E., Cinelli, A.R., Bertorello, A.M., and Pedemonte, C.H. Intracellular Na+ regulates dopamine- and angiotensin II- receptors availability at the plasma membrane and their cellular responses in renal epithelia. J. Biol. Chem., 2003, 278, 28719–28726
- Yudowski, G.A., Efendiev, R., Pedemonte, C.H., Katz, A.I., Bergren, P.O., and Bertorello, A.M. Phosphoinositide-3 kinase binds to a proline-rich motif in the Na,K-ATPase alpha subunit and regulates its trafficking. Proc. Natl. Acad. Sci. U S A, 2000, 97, 6556-6561
- Efendiev, R., Bertorello, A.M., Zandomeni, R., Cinelli, A.R., and Pedemonte, C.H. Agonist-dependent regulation of renal Na,K-ATPase activity is modulated by intracellular sodium concentration. J. Biol. Chem., 2002, 277, 11489-11496
- Efendiev, R., Yudowski, G.A., Mendez, C.F., Zwiller, J., Cotta Done, S., Leibiger, B., Katz, A., Berggren, P.-O., Pedemonte, C.H., Leibiger I.B., and Bertorello, A.M. Relevance of dopamine signals anchoring dynamin-2 to the plasma membrane during Na,K-ATPase endocytosis. J. Biol. Chem., 2002, 277, 44108-44114
Riad Efendi , Ph.D.
Assistant Professor
UTHSC, Medical School, (713) 500 - 6854
Riad.Efendi@uth.tmc.edu
Signal transduction mediation by kinases
My research focuses on elucidating how signaling pathways are organized within different cell types. Understanding of how general transduction pathways are tailored to cell-specific functions through compartmentalization of signaling proteins with anchoring and scaffolding proteins may be a key to insights into unique functions of these cells. Particularly, my interest encompasses members of the A-kinase anchoring protein (AKAP) superfamily, which by coupling protein kinase A with different adenylyl cyclase isoforms, provide a molecular mechanism for cAMP compartmentalization. AKAPs are known to control glutamate signaling in the brain and regulate cardiac and skeletal muscle Ca2+ channels. By using molecular biology, protein chemistry, fluorescence microscopy and functional studies to investigate AKAPs’ central place in PKA signaling, my research will yield important insights into the role of compartmentalized cAMP signaling in cardiac muscle and pathologies associated with it.
Another major object of my interest is the mechanism by which different isozymes of protein kinase C mediate endocytosis or recruitment to the plasma membrane of Na,K-ATPase, dopamine and angiotensin II receptors, and effect of the intracellular sodium concentration on these processes. Translocation of these membrane proteins regulates renal sodium reabsorption, a major contributor to blood pressure. Elucidation of this molecular mechanism will aid in the design of new drugs that target pathological conditions associated with the elevated blood pressure.
