Martin J. Lohse

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Martin J. Lohse (born 26 August 1956) is a German physician and pharmacologist.

Contents

Career

Lohse performs ongoing research on G protein-coupled receptors. Since 1993, he is a Professor of Pharmacology at the University of Würzburg, Germany, retired in 2022, and he was the Founding Chairman of the Rudolf Virchow Center (2001–2016). From 2016 to 2019, he was Chairman of the Board and Scientific Director of the Max Delbrück Center in Berlin, a national research center of the Helmholtz Association for molecular medicine. [1] [2] In 2017, he also became Speaker of the Board of the Berlin Institute of Health, a joint research center of the Max Delbrück Center and the Charité. Since 2020 he is chairman and managing director of ISAR Bioscience Institute, a translational research institute in Planegg/Munich.

Lohse received his exam in medicine as well as his M.D. from the University of Göttingen, and did research in pharmacology at the University of Heidelberg, Duke University and the GeneCenter in Munich. His research focusses on the role of receptors in heart failure and on the mechanisms of their activation and inactivation.

While working with Robert Lefkowitz at Duke University he discovered beta-arrestins, proteins that regulate the function of certain cell surface receptors. [3] He discovered that beta-1 adrenergic receptors and their regulatory G protein-coupled receptor kinases are dysregulated in heart failure. [4] The observation that increased β1-adrenergic receptor levels and signaling cause long-term cardiac damage contributed to the use of beta-blockers in heart failure patients. [5] Further studies by his lab showed that heart failure is accompanied by a specific type of activation of so-called ERK protein kinases (Extracellular signal-regulated kinases). [6] Another regulatory protein, Raf kinase inhibitor protein (RKIP), was shown to exert beneficial effects on cardiac structure and function. [7] Lohse pioneered the use of optical techniques to determine, where and how fast receptors become activated by hormones and neurotransmitters. [8] [9] [10] These studies led to the concept of nanometer-sized independent domains where signaling by individual receptors occurs. [11] [12]

Awards

He was awarded the Leibniz Award in 1999, the Ernst Jung Award for Medicine in 2000, and the Research Achievement Award of the International Society of Heart Research in 2007. From 2003 until 2008 he was a member of the German National Ethics Council. From 2009 to 2015 he was Vice President for Research of the University of Würzburg. From 2009 to 2019, he was Vice President of the German Academy of Sciences Leopoldina. [13] [14] From 2019 to 2022 he served as President of the Society of German Natural Scientists and Physicians and organized its 200-year anniversary meeting in Leipzig in 2022. [15]

Related Research Articles

<span class="mw-page-title-main">G protein-coupled receptor</span> Class of cell surface receptors coupled to G-protein-associated intracellular signaling

G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops or to the binding site within transmembrane helices. They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.

<span class="mw-page-title-main">Adrenergic receptor</span> Class of G protein-coupled receptors

The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.

<span class="mw-page-title-main">Penbutolol</span> Chemical compound

Penbutolol is a medication in the class of beta blockers, used in the treatment of high blood pressure. Penbutolol is able to bind to both beta-1 adrenergic receptors and beta-2 adrenergic receptors, thus making it a non-selective β blocker. Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors.

<span class="mw-page-title-main">Beta-1 adrenergic receptor</span> Protein-coding gene in the species Homo sapiens

The beta-1 adrenergic receptor, also known as ADRB1, can refer to either the protein-encoding gene or one of the four adrenergic receptors. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein that is expressed predominantly in cardiac tissue. In addition to cardiac tissue, beta-1 adrenergic receptors are also expressed in the cerebral cortex.

<span class="mw-page-title-main">Beta-2 adrenergic receptor</span> Mammalian protein found in humans

The beta-2 adrenergic receptor, also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that binds epinephrine (adrenaline), a hormone and neurotransmitter whose signaling, via adenylate cyclase stimulation through trimeric Gs proteins, increases cAMP, and, via downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation.

<span class="mw-page-title-main">Arrestin</span> Family of proteins

Arrestins are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors (GPCRs) in the visual rhodopsin system by Hermann Kühn, Scott Hall, and Ursula Wilden and in the β-adrenergic system by Martin J. Lohse and co-workers.

<span class="mw-page-title-main">G protein-coupled receptor kinase 2</span> Enzyme

G-protein-coupled receptor kinase 2 (GRK2) is an enzyme that in humans is encoded by the ADRBK1 gene. GRK2 was initially called Beta-adrenergic receptor kinase, and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK3(βARK2).

Gq protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gq/11 (Gq/G11) family or Gq/11/14/15 family to include closely related family members. G alpha subunits may be referred to as Gq alpha, Gαq, or Gqα. Gq proteins couple to G protein-coupled receptors to activate beta-type phospholipase C (PLC-β) enzymes. PLC-β in turn hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 acts as a second messenger to release stored calcium into the cytoplasm, while DAG acts as a second messenger that activates protein kinase C (PKC).

<span class="mw-page-title-main">PRKCE</span> Protein-coding gene in the species Homo sapiens

Protein kinase C epsilon type (PKCε) is an enzyme that in humans is encoded by the PRKCE gene. PKCε is an isoform of the large PKC family of protein kinases that play many roles in different tissues. In cardiac muscle cells, PKCε regulates muscle contraction through its actions at sarcomeric proteins, and PKCε modulates cardiac cell metabolism through its actions at mitochondria. PKCε is clinically significant in that it is a central player in cardioprotection against ischemic injury and in the development of cardiac hypertrophy.

<span class="mw-page-title-main">RGS2</span> Protein-coding gene in the species Homo sapiens

Regulator of G-protein signaling 2 is a protein that in humans is encoded by the RGS2 gene. It is part of a larger family of RGS proteins that control signalling through G-protein coupled receptors (GPCR).

<span class="mw-page-title-main">Arrestin beta 2</span> Protein-coding gene in the species Homo sapiens

Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ARRB2 gene.

<span class="mw-page-title-main">Arrestin beta 1</span> Human protein and coding gene

Arrestin, beta 1, also known as ARRB1, is a protein which in humans is encoded by the ARRB1 gene.

<span class="mw-page-title-main">GRK5</span> Protein-coding gene in the species Homo sapiens

G protein-coupled receptor kinase 5 is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases, and is most highly similar to GRK4 and GRK6. The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.

In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication.

<span class="mw-page-title-main">Beta-adrenergic agonist</span> Medications that relax muscles of the airways

Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. They are a class of sympathomimetic agents, each acting upon the beta adrenoceptors. In general, pure beta-adrenergic agonists have the opposite function of beta blockers: beta-adrenoreceptor agonist ligands mimic the actions of both epinephrine- and norepinephrine- signaling, in the heart and lungs, and in smooth muscle tissue; epinephrine expresses the higher affinity. The activation of β1, β2 and β3 activates the enzyme, adenylate cyclase. This, in turn, leads to the activation of the secondary messenger cyclic adenosine monophosphate (cAMP); cAMP then activates protein kinase A (PKA) which phosphorylates target proteins, ultimately inducing smooth muscle relaxation and contraction of the cardiac tissue.

<span class="mw-page-title-main">G beta-gamma complex</span>

The G beta-gamma complex (Gβγ) is a tightly bound dimeric protein complex, composed of one Gβ and one Gγ subunit, and is a component of heterotrimeric G proteins. Heterotrimeric G proteins, also called guanosine nucleotide-binding proteins, consist of three subunits, called alpha, beta, and gamma subunits, or Gα, Gβ, and Gγ. When a G protein-coupled receptor (GPCR) is activated, Gα dissociates from Gβγ, allowing both subunits to perform their respective downstream signaling effects. One of the major functions of Gβγ is the inhibition of the Gα subunit.

Heterologous desensitization is the term for the unresponsiveness of cells to one or more agonists to which they are normally responsive. Typically, desensitization is a receptor-based phenomenon in which one receptor type, when bound to its ligand, becomes unable to further influence the signalling pathways by which it regulates cells and, in the case of cell surface membrane receptors, may thereafter be internalized. The desensitized receptor is degraded or freed of its activating ligand and re-cycled to a state where it is again able to respond to cognate ligands by activating its signalling pathways.

<span class="mw-page-title-main">G protein-coupled receptor kinase 3</span> Protein-coding gene in the species Homo sapiens

G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ADRBK2 gene. GRK3 was initially called Beta-adrenergic receptor kinase 2 (βARK-2), and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK2.

Beta adrenergic receptor kinase carboxyl-terminus is a peptide composed of the last 194 amino acid residues of the carboxyl-terminus of beta adrenergic receptor kinase 1 (βARK1). It binds the βγ subunits of G proteins located in the plasma membrane of cells. It is currently an experimental gene therapy for the treatment of heart failure.

The Raf kinase inhibitor protein (RKIP) is a kinase inhibitor protein, that regulates many signaling pathways within the cell. RKIP is a member of the phosphatidylethanolamine-binding protein family and has displayed disruptive regulation on the Raf-1-MEK1/2, ERK1/2 and NF-kappaB signalling pathways, by interaction with the Raf-1 kinase.

References

  1. ↑ "Martin Lohse wird Chef des Max-Delbrück-Centrums". Gesundheitsstadt Berlin (in German). 4 March 2016. Retrieved 27 November 2021.
  2. ↑ "Wechsel im Vorstand des MDC". MDC Berlin (in German). Retrieved 27 November 2021.
  3. ↑ Lohse, Martin J.; Benovic, Jeffrey L.; Codina, Juan; Caron, Marc G.; Lefkowitz, Robert J. (22 June 1990). "β-Arrestin: a Protein that Regulates β-adrenergic Receptor Function". Science. 248 (4962). American Association for the Advancement of Science (AAAS): 1547–1550. Bibcode:1990Sci...248.1547L. doi:10.1126/science.2163110. ISSN   0036-8075. PMID   2163110.
  4. ↑ Ungerer, M; Böhm, M; Elce, J S; Erdmann, E; Lohse, M J (1993). "Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart". Circulation. 87 (2). Ovid Technologies (Wolters Kluwer Health): 454–463. doi: 10.1161/01.cir.87.2.454 . ISSN   0009-7322. PMID   8381058.
  5. ↑ Engelhardt, S.; Hein, L.; Wiesmann, F.; Lohse, M. J. (8 June 1999). "Progressive hypertrophy and heart failure in 1-adrenergic receptor transgenic mice". Proceedings of the National Academy of Sciences. 96 (12): 7059–7064. doi: 10.1073/pnas.96.12.7059 . ISSN   0027-8424. PMC   22055 . PMID   10359838.
  6. ↑ Lorenz, Kristina; Schmitt, Joachim P; Schmitteckert, Eva M; Lohse, Martin J (7 December 2008). "A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy". Nature Medicine. 15 (1). Springer Science and Business Media LLC: 75–83. doi:10.1038/nm.1893. ISSN   1078-8956. PMID   19060905. S2CID   13973823.
  7. ↑ Schmid, Evelyn; Neef, Stefan; Berlin, Christopher; Tomasovic, Angela; Kahlert, Katrin; Nordbeck, Peter; Deiss, Katharina; Denzinger, Sabrina; Herrmann, Sebastian; Wettwer, Erich; Weidendorfer, Markus; Becker, Daniel; Schäfer, Florian; Wagner, Nicole; Ergün, Süleyman; Schmitt, Joachim P; Katus, Hugo A; Weidemann, Frank; Ravens, Ursula; Maack, Christoph; Hein, Lutz; Ertl, Georg; Müller, Oliver J; Maier, Lars S; Lohse, Martin J; Lorenz, Kristina (19 October 2015). "Cardiac RKIP induces a beneficial β-adrenoceptor–dependent positive inotropy". Nature Medicine. 21 (11). Springer Science and Business Media LLC: 1298–1306. doi:10.1038/nm.3972. ISSN   1078-8956. PMID   26479924. S2CID   11418537.
  8. ↑ Vilardaga, Jean-Pierre; Bünemann, Moritz; Krasel, Cornelius; Castro, Mariàn; Lohse, Martin J (15 June 2003). "Measurement of the millisecond activation switch of G protein–coupled receptors in living cells". Nature Biotechnology. 21 (7). Springer Science and Business Media LLC: 807–812. doi:10.1038/nbt838. ISSN   1087-0156. PMID   12808462. S2CID   19520338.
  9. ↑ Hoffmann, Carsten; Gaietta, Guido; Bünemann, Moritz; Adams, Stephen R; Oberdorff-Maass, Silke; Behr, Björn; Vilardaga, Jean-Pierre; Tsien, Roger Y; Ellisman, Mark H; Lohse, Martin J (17 February 2005). "A FlAsH-based FRET approach to determine G protein–coupled receptor activation in living cells". Nature Methods. 2 (3). Springer Science and Business Media LLC: 171–176. doi:10.1038/nmeth742. ISSN   1548-7091. PMID   15782185. S2CID   6405686.
  10. ↑ Lohse, Martin J.; Nuber, Susanne; Hoffmann, Carsten (8 March 2012). Christopoulos, Arthur (ed.). "Fluorescence/Bioluminescence Resonance Energy Transfer Techniques to Study G-Protein-Coupled Receptor Activation and Signaling". Pharmacological Reviews. 64 (2). American Society for Pharmacology & Experimental Therapeutics (ASPET): 299–336. doi:10.1124/pr.110.004309. ISSN   0031-6997. PMID   22407612. S2CID   2042851.
  11. ↑ A. Bock, P. Annibale, C. Konrad, A. Hannawacker, S.E. Anton, I. Maiellaro, U. Zabel, S. Sivaramakrishnan, M. Falcke, M.J. Lohse: "Optical mapping of cAMP signaling at the nanometer scale." In: Cell. 182, 2020, pp. 1519-1530.
  12. ↑ S.E. Anton, C. Kayser, I. Maiellaro, K. Nemec, J. Möller, A. Koschinski, M. Zaccolo, P. Annibale, M. Falcke, M.J. Lohse, A. Bock: "Receptor-associated independent cAMP nanodomains mediate spatiotemporal specificity of GPCR signaling." In: Cell. 185, 2022, pp. 1130-1142.
  13. ↑ "Martin J. Lohse re-elected as Vice-President of the Leopoldina". Nationale Akademie der Wissenschaften Leopoldina. 6 October 2021. Retrieved 27 November 2021.
  14. ↑ "Curriculum Vitae Prof. Dr. Martin J. Lohse" (PDF). www.leopoldina.org. Retrieved April 23, 2024.
  15. ↑ Martin Lohse (Ed.): 'When the spark is lit. 200 years of the Society of German Natural Scientists and Physicians.' (in German) Passage-Verlag, Leipzig 2022, ISBN 978-3-95415-130-1
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