Phospholipid signaling in platelet and T-cells.
Key words: Pleckstrin, PH domains, cytoskeleton.
Description of Research
Inappropriate platelet activation contributes to vascular diseases including stroke and myocardial ischemia. Our laboratory is focused on phospholipid signaling in platelets and its contribution to inappropriate platelet activation. Ongoing projects are directed at understanding the roles of pleckstrin and lipid kinases in platelets. Pleckstrin (p47) was once solely known as an early marker of platelet activation; more recently it has been noted to contain the prototypic Pleckstrin Homology motif. Over the past half dozen years, work derived from our laboratory has demonstrated that pleckstrin plays a dominant role in the reorganization of the platelet, and lymphocyte, cytoskeleton. Furthermore, our laboratory has established these effects are regulated by pleckstrin phosphorylation, require critical lipid-binding residues contained with the amino-terminal Pleckstrin Homology domain, and have implicated an effector for this process to be the small GTP-binding protein, Rac. Additional work from our laboratory has helped define the role of phospholipid kinases in the pathway that is initiated by G-protein coupled receptors and ultimately leads to actin reorganization. Our studies use molecular and cellular biologic techniques to examine blood cell biology, and involve expression mutagenesis, single cell microinjection, genetic library screening, and murine homologous gene targeting ("gene knock-out").
pleckstrin2 and actin assembly
PIP5K Ig and focal adhesions
Andrew Louden - Postdoctoral Fellow
Feng Wang - Postdoctoral Fellow
Seun-Ah Yang - Postdoctoral Fellow
Tami Bach - Postdoctoral Fellow
Michael Hu - Technician
Lurong Lian - Technician
Qing Chen - Undergraduate Student
Wang, Y., Chen, X., Lian, L., Bach, T.L., Golden, J., Morrisey, E.M., Abrams, C.S.: PIP5K? is required for cardiovascular and neuronal development Proceedings of the National Academy of Science (U.S.A.) 104 (28): 11748-53,2007.
Trivedi, C.M., Luo, Y., Yin, Z., Zhang, M., Floss, T., Goettlicher, M., Ruiz, P., Wurst, W., Ferrari, V., Abrams, C.S., Gruber, P., Epstein, J.A.: HDAC2 regulates the cardiac hypertrophic response by modulating GSK3ß activity Nature Medicine 13 : 324-331,2007.
Wang, Y., Chen, X., Lian, L., Tang, T., Stalker, T.J., Sasaki, T., Brass, L.F., Choi, J.K., Hartwig, J.H., Abrams, C.S.: Loss of PIP5KIß demonstrates that rapid PIP2 synthesis is required for IP3 formation Proceedings of the National Academy of Science (U.S.A.) 105 : 14064-14069,2008.
Pan, W., Choi, S.-C., Wang, H., Qin, Y., Volpicelli-Daley, L., Swan, L., Lucast, L., Khooo, C., Zhang, X., Li, L., Abrams, C.S., Sokol, S.Y., Wu, D.: Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation Science 321 : 1350-1353,2008.
Wang, Y., Litvinov, R.I., Chen, X., Lian, L., Bach, T.L., Petrich, B., Monkley, S., Critchley, D., Birnbaum, M.J., Weisel, J.W., Hartwig, J.H., Abrams, C.S.: Loss of PIP5K?, but not PIP5Kß, impairs the integrity of the membrane cytoskeleton J. Clinical Investigation 118 (2): 812-819,2008.
Mao, Y.S., Yamaga, M., Zhu, X., Wei, M., Sun, H.-Q., Wang, J., Yun, M., Wang, Y., Di Paolo, G., Bennett, M., Mellman, I.S., Abrams, C.S., De Camilli, P.V., Lu, C.Y., and Yin, H.L.: Essential and unique roles of PIP5K? and a in Fc? receptor-mediated phagocytosis J. Cell Biology Journal of Cell Biology 184 : 281-296,2009.
Lian, L., Wang, W., Flick, M., Choi, J., Scott, E., Degen, J., Lemmon, M.A., Abrams, C.S.: Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis Blood In press : 2009.
Min, S.H., Abrams, C.S.: Why do phosphatidylinositol kinases have so many isoforms? Biochemical J 423 (1): 99-108,2009.
Volpicelli-Daley, L.A., Lucast, L., Gong, L.-W., Liu, L., Sasaki, J., Sasaki, T., Abrams, C.S., Kanaho, Y., De Camilli, P.: Phosphatidylinositol 4-phosphate 5-kinases (PIPKIs) and phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] synthesis in the brain. J. Biologic Chemistry : 28708-14,2010.
Mitsios, J.V., Prévost, N., Kasirer-Friede, A., Gutierrez, E., Groisman, A., Abrams, C.S., Litvinov, R.I., Zemljic-Harpf, A., Ross, R.S., Shattil, S., J.: What is vinculin needed for in platelets? J. Thrombosis & Haemostasis : 2294-2304,2010.
View all publications