Rick Cerione

<TITLE>Richard A. Cerione</TITLE> <CENTER><TABLE BORDER=0 ALIGN=CENTER VALIGN=TOP CELLPADDING=10> <TR> <TD VALIGN=TOP><table border=3 cellpadding=1><tr><td><IMG Align=TOP SRC="cerione_picture1.JPEG" ></td></tr></table></TD> <TD VALIGN=MIDDLE><B><H2><CENTER>Richard A. Cerione</CENTER></H2><HR> <H3>Professor of Pharmacology<BR> <A HREF="../MolecMed.html">Department of Molecular Medicine</A><BR> College of Veterinary Medicine<BR> Cornell University</H3></TD> </TR> </TABLE> </CENTER> <HR> <BR> <Strong>Signal Transduction Mechanisms</Strong> <P> We are studying the molecular mechanisms by which signals are transmitted from receptor proteins on the surface of cell membranes to specified biological effectors. At the present time two general areas are being investigated in the laboratory; one being the rhodopsin-coupled visual transduction system, the other involving growth factor receptor/tyrosine kinases. We are using the visual system to probe the mechanisms underlying the activation and deactivation of G protein transducers. Each of the primary components of this system (i.e., the receptor, rhodopsin; the G protein, transducin; and the effector enzyme, the cyclic GMP phosphodiesterase) can be isolated in mg quantities, moreover, the interactions which occur between these components can be reconstituted in phospholipid vesicle systems. A variety of fluorescence spectroscopic, steady state kinetic and immunological approaches are being used in conjunction with reconstitution studies to probe the essential functional domains on the G protein, transducin, which are involved in its regulatory action. Studies are also underway to examine the abilities of various mutated forms of the different subunits of the G protein to elicit regulatory responses within the visual cascade. <P> Various lines of approach are also being used to delineate the steps involved in growth factor-coupled signal transduction. A number of growth factor receptor/tyrosine kinases are being studied, including the epidermal growth factor receptor, neu, and the erbB3 protein. One question of interest pertains to the role of receptor-receptor interactions in triggering the tyrosine kinase activities of these receptors. This issue is being addressed by using fluorescence resonance energy transfer approaches to monitor receptor-receptor interactions in living cells. Molecular biological approaches are being used to over-express the different tyrosine kinases for protein chemical, biophysical, and site-directed mutagenic studies. Transfection of the cDNA for this domain into various cells is also being performed to examine roles of various regions of the tyrosine kinase domain in directing cell growth and proliferation. <P> Finally, the roles of GTP-binding proteins in cell-cycle-regulation are being examined. One project receiving particular emphasis is the ras-like protein CDC42 which is the human homolog of a yeast cell-division-cycle protein. We recently have identified three classes of regulators for this GTP-binding protein. One class, the GTPase-activating proteins (GAPs), comprise a number of proteins suspected to be involved in cell growth regulation including the breakpoint cluster region protein (bcr) and the ras-GAP-binding protein, p190. Another class of regulators includes the DBL oncogene product which serves to stimulate the guanine nucleotide exchange activity of CDC42. Expression systems have been established for CDC42 and its different regulatory proteins and we are in the process of mapping essential domains on the individual proteins. A collaborative project with Robert Oswald and his colleagues aimed at obtaining 3D structure information for CDC42 and its regulators also is underway. <P> <A HREF = "Cerione_CV.html">Curriculum vitae and selected publications</A><BR><P> <CENTER><A HREF = "../cornell_pharmacology.html">Field of Pharmacology Home Page</A></CENTER> <BR> <HR> <BR> <TABLE BORDER=0 ALIGN=LEFT VALIGN=TOP CELLPADDING=5> <TR> <TD VALIGN=TOP><IMG Align=Top SRC="../faculty_pictures/cerione_low.jpeg"></A></TD> <TD VALIGN=MIDDLE> <PRE>Rick Cerione Department of Pharmacology C3 155 Veterinary Medical Center College of Veterinary Medicine Cornell University Ithaca, New York 14853 USA <a href=mailto:rac1@cornell.edu>e-mail</a>: rac1@cornell.edu phone: 607-253-3888 FAX: 607-253-3659 </PRE> </TD> </TR> </TABLE>