Raymond L. Erikson

Department of Molecular and Cellular Biology
Harvard University
Biological Laboratories 244

16 Divinity Avenue
Cambridge, MA 02138
tel: (617) 495-5386 fax: (617) 495-0681 
Erikson Home Page

Reversible protein phosphorylation and cell proliferation

The Erikson laboratory studies different signaling pathways and/or protein kinase subfamilies that influence mammalian cell proliferation. One pathway is the well-known MAP kinase cascade. Recently we have focused on the protein kinase activator of MAP kinase, Mek, which was cloned in our laboratory about three years ago. The protein kinase Raf1 activates Mek by phosphorylation of two serine residues in subdomain VIII of the catalytic region of the enzyme. Substitution of aspartate or glutamate residues at these sites results in a remarkable 6000-fold increase of Mek activity. The biological consequences of these mutations are under study but preliminary results show that certain Mek phosphorylation site mutants transform NIH 3T3 cells.

In addition, we study a subfamily of murine protein kinases, dubbed polo-like-kinases. At least one of these enzymes, Plk1, acts late in the cell-cycle and appears to be required in anaphase and cytokinesis. Plk1 interacts strongly with polar microtubules at this stage of the cell cycle and is associated with a mitotic-specific kinesin. Identification of its substrates and elucidation of its mechanism of activation are in progress. We have also recently purified and sequenced a novel protein kinase that is not activated by commonly studied mitogens but is activated very rapidly by agents that induce apoptosis in cultured cells. Molecular clones of this protein kinase will be used to determine its function in the response of cells to stress.

Selected Publications:

Brott, B.K., Pinsky, B.A. and Erikson, R.L.:  Nlk is a murine protein kinase related to Erk/MAP kinases and localized in the nucleus. Proc. Natl. Acad. Sci. USA 95: 963-968, 1998.

Greulich, H. and Erikson, R.L.:  An analysis of Mek1 signaling in cell proliferation and transformation.  J. Biol. Chem. 273: 13280-13288, 1998.

Lee, K.S., Grenfell, T.Z., Yarm, F.R. and Erikson, R.L.: Mutation of the polo-box disrupts localization and mitotic functions of the mammalian polo kinase Plk.  Proc. Natl. Acad. Sci. USA 95:9301-9306, 1998.