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Rick Stouffer
| Email: | rick_stouffer@med.unc.edu |
|---|---|
| Appointments: |
Distinguished Professor |
| Room: | Cath Lab 2227 Old Infirmary |
| Phone: | (919) 843-4591 |
The long-term goal of my research is to explore the cellular and molecular mechanisms that control growth regulation of vascular cells. Excessive proliferation, migration and hypertrophy of vascular smooth muscle cells (SMC) plays a major role in the development of atherosclerotic plaques and in limiting the long term success of revascularization procedures such as coronary artery bypass grafting and percutaneous coronary interventions. Our current research effort is focused on understanding the role of avb3 integrins in regulating intracellular signaling in SMC. We are interested in how integrins transduce signals and have found that the cytoskeletal protein nonmuscle myosin-A (NM-A) rapidly associated with avb3 and with focal adhesion kinase (FAK) following treatment of rat aortic SMC with a-thrombin. While myosin has traditionally been thought of primarily as a molecular motor, newer evidence implicates myosin in diverse cellular functions. Based on published evidence and our studies, our conception of myosin is changing to include a role in regulating focal adhesion formation and thereby signal transduction. This situation is analogous to integrin biology; originally conceived simply as adhesion molecules, integrins are now realized to transduce signals, elicit gene transcription and regulate cellular responses.
NM-A provides a unique site for regulation as two distinct conformations exist in equilibrium: a folded state in which myosin can not assemble into filaments (i.e. 10S conformation) and an extended conformation that promotes the assembly of filaments and binding to other proteins (i.e. 6S). Equilibration between 6S and 10S is primarily regulated by phosphorylation of myosin light chain (MLC). Thus phosphorylation of MLC, which is stimulated by PAR-1, could play an important regulatory role in integrin-mediated signaling in response to activation of G protein-coupled receptors.
NM-A provides a unique site for regulation as two distinct conformations exist in equilibrium: a folded state in which myosin can not assemble into filaments (i.e. 10S conformation) and an extended conformation that promotes the assembly of filaments and binding to other proteins (i.e. 6S). Equilibration between 6S and 10S is primarily regulated by phosphorylation of myosin light chain (MLC). Thus phosphorylation of MLC, which is stimulated by PAR-1, could play an important regulatory role in integrin-mediated signaling in response to activation of G protein-coupled receptors.