Dr. GPCR Ecosystem
New structural perspectives in G protein-coupled receptor-mediated Src family kinase activation
Abstract
The activation of Src family kinases (SFKs) can occur via multiple signaling pathways, yet many of them are poorly understood. The G protein-coupled receptor (GPCR)-mediated regulation of SFKs can occur through a direct interaction between both proteins or be allosterically regulated by arrestins and G proteins. A rearrangement of binding motifs within the active conformation of arrestin-3 mediates Src regulation could be a key regulator. By comparison of available crystal structures, we hypothesize a potentially different activation mechanism compared to arrestin-2. Furthermore, we discuss the probable direct regulation of SFK by GPCRs and investigate the intracellular domains of exemplary GPCRs with conserved polyproline binding motifs, that might serve as scaffolding domains to allow such direct interaction. Large intracellular domains in GPCRs are often understudied and in general, not much of their contribution to different signaling pathways is known. The suggested direct interaction between a GPCR and an SFK could allow for a potential immediate allosteric regulation of SFKs by GPCRs and thereby unravel a novel mechanism for SFK signaling.
About Dr. Sandra Berndt
Dr. Sandra Berndt is a research group leader in the Rudolf Schönheimer Institute of Biochemistry, Leipzig University, Germany.
She received her Doctorate in Natural Sciences (Biochemistry) from the University of Leipzig in Germany. Her work focused on the structural and dynamical characterization of a class A G protein-coupled receptor upon ligand binding using NMR spectroscopy. Afterward, she was a postdoctoral fellow in the Department of Biochemistry at Cambridge University in the UK. Here she continued her work with G protein-coupled receptors using NMR. She completed a second postdoctoral training in the Department of Pharmacology at Vanderbilt University, Nashville, USA, in the laboratories of Prof. Tina Iverson and Prof. Vsevolod Gurevich. Here she was working on cellular signaling of GPCRs, specifically arrestin mediated signaling. Her main research was addressed towards the understanding of the interaction between Src family kinases and arrestins. This work she continues with her group, where she is focusing on the direct interaction of GPCRs with different Src family kinases.
Dr. Sandra Berndt on the web
