Deborah K. Morrison, Ph.D.
Laboratory of Cell and Developmental Signaling
Advanced Technology Research Facility, D3027 Frederick, MD 21701
Regulation of Signal Transduction Pathways
The proliferative state of normal cells is precisely regulated by signals received from the extracellular environment. Understanding how these signals are relayed from the cell surface to the nucleus is the major objective of the Cellular Growth Mechanisms Section. Studies in this area are particularly relevant to cancer research because release from regulatory controls at any point along the signaling cascade can result in uncontrolled cell growth or oncogenesis. We have chosen to focus our studies on the pathway regulated by the Ras GTPase, where our aims are to further elucidate the processes involved in signal transduction and to identify critical regulatory points linked to tumor formation.
The transmission of growth and developmental signals from the membrane to the nucleus requires the coordinated action of a diverse set of proteins. Previous work from our laboratory and others has demonstrated that the Raf serine/threonine kinases serve as central intermediates in many signaling pathways, functioning downstream of activated tyrosine kinases and Ras and upstream of mitogen-activated protein kinase (MAPK) and MAPK kinase (MKK or MEK). A major goal of our research has been to elucidate the mechanisms regulating Raf activity, with a particular emphasis on understanding the role that phosphorylation events and protein interactions play in Raf regulation.
Our laboratory's research efforts have also focused on scaffold proteins involved in signal transduction, such as the kinase suppressor of Ras (KSR) family. KSR was originally identified in Drosophila and C. elegans and is an evolutionarily conserved component of the Ras pathway. Our studies examining the mammalian KSR proteins are directed towards determining the function and regulation of these scaffolds in cell signaling.
Finally, our laboratory has had an ongoing interest in using mass spectrometry to analyze signaling complexes. By taking a proteomics approach, we hope to identify new components involved in Ras-dependent signal transduction.
Ritt DA, Abreu-Blanco MT, Bindu L, Durrant DE, Zhou M, Specht SI, Stephen AG, Holderfield M, Morrison DK. Inhibition of Ras/Raf/MEK/ERK Pathway Signaling by a Stress-Induced Phospho-Regulatory Circuit. Mol Cell. 2016;64(5):875-887.
Lim J, Ritt DA, Zhou M, Morrison DK. The CNK2 scaffold interacts with vilse and modulates Rac cycling during spine morphogenesis in hippocampal neurons. Curr Biol. 2014;24(7):786-92.
Freeman AK, Ritt DA, Morrison DK. Effects of Raf dimerization and its inhibition on normal and disease-associated Raf signaling. Mol Cell. 2013;49(4):751-8.
Lim J, Zhou M, Veenstra TD, Morrison DK. The CNK1 scaffold binds cytohesins and promotes insulin pathway signaling. Genes Dev. 2010;24(14):1496-506.
Dougherty MK, Müller J, Ritt DA, Zhou M, Zhou XZ, Copeland TD, Conrads TP, Veenstra TD, Lu KP, Morrison DK. Regulation of Raf-1 by direct feedback phosphorylation. Mol Cell. 2005;17(2):215-24.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on March 11th, 2021