SULEIMAN W. BAHOUTH, Ph.D., M.S., B.S.

Professor
Pharmacology
Adjunct Professor
Pharmaceutical Sciences

Office: 210J TRANSLATIONAL RESEARCH BUILDING
71 SOUTH MANASSAS
MEMPHIS TN 38163
Tel: (901) 448-1503
sbahouth@uthsc.edu

Education

  • Pharm.D., New York University, School of Medicine, Dept. of Pharmacology, New York, Pharmacology
  • M.S., New york University, School of Medicine, Dept. of Pharmacology, New York, Pharmacology
  • M.S., George Washintong University, School of Medicine, Dept. of Pharmacology, Washington D.C., Pharmacology
  • M.S., American University of Beirut, Lebanon, Beirut, Pharmacology
  • B.S., American University of Beirut, Lebanon, Beirut, Pharmacology

Roadmap for G protein coupled receptor trafficking in mammalian cells

Roadmap

A, Organization of membranous ß1-AR mutants and chimeras. Left hand side panel, wildtype or ß1-AR-chimeras with a type-I PDZ that bind to SAP97 (blue PDZ) assemble as a complex composed of SAP97/AKAP79/PKA.  Activation of these GPCR increases cyclic AMP, which promotes the dissociation of the catalytic subunit of PKA from PDZ-bound PKA.   The catalytic subunit of PKA phosphorylates Ser312 in the 3rd intracellular loop to imprint the recycling signal onto the ß1-AR (“red” P).  Middle panel, ß1-AR-chimeras with an inactive PDZ or with a type-I PDZ that did bind SAP97 (red PDZ), did not assemble a SAP97-anchored complex.  Right hand panel, ß1-AR-chimeras with non-PDZ recycling sequences, do not assemble a complex (black PDZ).  Activation of all of these receptors however, increased cyclic AMP and promoted the binding of ß-arrestin to the GRK-phosphorylated GPCR. In the left hand side panel, We hypothesize that acidic amino acids at p = -3 in wildtype or ß1-AR mutants would interact with ß-arrestin to promote the dissociation of the complex anchored at the PDZ prior to the internalization of the various GPCR into early endosomes, while PDZs with neutral residues at p = -3 are internalized with their “PDZ binding protein” (± PBP).  B, Trafficking roadmap of internalized ß1-AR mutants and chimeras. Left hand side panel, illustrates the trafficking roadmap of ß1-AR mutants with a phospho-Ser312.  These GPCR traffic by a process termed “sequence-dependent” trafficking, in which they are “sorted” from early endosomes into membrane extensions (“blue” arrow) that coalesce into “recycling endosomes”. Middle panel, illustrates that ß1-AR with type-I PDZs, but without a phospho-Ser312, were retained within the “body’ of early endosomes.  These early endosomes eventually matured into late endosomes/ lysosomes, in which the retained “cargo” is eventually degraded. Right hand panel, indicates that internalized ß1-AR with recycling non-PDZ’s traffic out of early endosomes into “recycling endosomes” by a process termed “bulk or sequence-independent” recycling.  ß1-AR-chimeras that traffic to  recycling endosomes” recycle back and fuse with the cell membrane (“green” arrows).

Publications

  1. Fain, JN, Buehrer, B, Bahouth, SW, Tichansky, DS, Madan, AK. Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue. Metabolism, 57 (7), 1005-15, 2008.
  2. Fain, JN, Sacks, HS, Buehrer, B, Bahouth, SW, Garrett, E, Wolf, RY, Carter, RA, Tichansky, DS, Madan, AK. Identification of omentin mRNA in human epicardial adipose tissue: comparison to omentin in subcutaneous, internal mammary artery periadventitial and visceral abdominal depots. Int J Obes (Lond), 32 (5), 810-5, 2008.
  3. Gardner, LA, Naren, AP, Bahouth, SW. Assembly of an SAP97-AKAP79-cAMP-dependent protein kinase scaffold at the type 1 PSD-95/DLG/ZO1 motif of the human beta(1)-adrenergic receptor generates a receptosome involved in receptor recycling and networking. J Biol Chem, 282 (7), 5085-99, 2007.
  4. Gardner, LA, Tavalin, SJ, Goehring, AS, Scott, JD, Bahouth, SW. AKAP79-mediated targeting of the cyclic AMP-dependent protein kinase to the beta1-adrenergic receptor promotes recycling and functional resensitization of the receptor. J Biol Chem, 281 (44), 33537-53, 2006.
  5. Zeitoun, O, Santos, NM, Gardner, LA, White, SW, Bahouth, SW. Mutagenesis within helix 6 of the human beta1-adrenergic receptor identifies Lysine324 as a residue involved in imparting the high-affinity binding state of agonists. Mol Pharmacol, 70 (3), 838-50, 2006.
  6. Delos Santos, NM, Gardner, LA, White, SW, Bahouth, SW. Characterization of the residues in helix 8 of the human beta1-adrenergic receptor that are involved in coupling the receptor to G proteins. J Biol Chem, 281 (18), 12896-907, 2006.
  7. Fain, JN, Bahouth, SW, Madan, AK. Involvement of multiple signaling pathways in the post-bariatric induction of IL-6 and IL-8 mRNA and release in human visceral adipose tissue. Biochem Pharmacol, 69 (9), 1315-24, 2005.
  8. Fain, JN, Madan, AK, Hiler, ML, Cheema, P, Bahouth, SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology, 145 (5), 2273-82, 2004.
  9. Gardner, LA, Delos Santos, NM, Matta, SG, Whitt, MA, Bahouth, SW. Role of the cyclic AMP-dependent protein kinase in homologous resensitization of the beta1-adrenergic receptor. J Biol Chem, 279 (20), 21135-43, 2004.
  10. Fain, JN, Bahouth, SW, Madan, AK. TNFalpha release by the nonfat cells of human adipose tissue. Int J Obes Relat Metab Disord, 28 (4), 616-22, 2004.
  11. Fain, JN, Bahouth, SW, Madan, AK. Haptoglobin release by human adipose tissue in primary culture. J Lipid Res, 45 (3), 536-42, 2004.
  12. Fain, JN, Kanu, A, Bahouth, SW, Cowan, GS, Lloyd Hiler, M. Inhibition of leptin release by atrial natriuretic peptide (ANP) in human adipocytes. Biochem Pharmacol, 65 (11), 1883-8, 2003.
  13. Fain, JN, Cheema, PS, Bahouth, SW, Lloyd Hiler, M. Resistin release by human adipose tissue explants in primary culture. Biochem Biophys Res Commun, 300 (3), 674-8, 2003.
  14. Kanu, A, Fain, JN, Bahouth, SW, Cowan, GS. Regulation of leptin release by insulin, glucocorticoids, G(i)-coupled receptor agonists, and pertussis toxin in adipocytes and adipose tissue explants from obese humans in primary culture. Metabolism, 52 (1), 60-6, 2003.
  15. Fain, JN, Kanu, A, Bahouth, SW, Cowan, GS, Hiler, ML, Leffler, CW. Comparison of PGE2, prostacyclin and leptin release by human adipocytes versus explants of adipose tissue in primary culture. Prostaglandins Leukot Essent Fatty Acids, 67 (6), 467-73, 2002.
  16. Bahouth, SW, Beauchamp, MJ, Vu, KN. Reciprocal regulation of beta(1)-adrenergic receptor gene transcription by Sp1 and early growth response gene 1: induction of EGR-1 inhibits the expression of the beta(1)-adrenergic receptor gene. Mol Pharmacol, 61 (2), 379-90, 2002.
  17. Bahouth, SW, Sowinski, KM, Lima, JJ. Regulation of human beta(1)-adrenergic receptors and their mRNA in neuroepithelioma SK-N-MC cells: effects of agonist, forskolin, and protein kinase A. Biochem Pharmacol, 62 (9), 1211-20, 2001.
  18. Fain, JN, Leffler, CW, Cowan, GS, Buffington, C, Pouncey, L, Bahouth, SW. Stimulation of leptin release by arachidonic acid and prostaglandin E(2) in adipose tissue from obese humans. Metabolism, 50 (8), 921-8, 2001.
  19. Fain, JN, Ballou, LR, Bahouth, SW. Obesity is induced in mice heterozygous for cyclooxygenase-2. Prostaglandins Other Lipid Mediat, 65 (4), 199-209, 2001.
  20. Cook, GA, Edwards, TL, Jansen, MS, Bahouth, SW, Wilcox, HG, Park, EA. Differential regulation of carnitine palmitoyltransferase-I gene isoforms (CPT-I alpha and CPT-I beta) in the rat heart. J Mol Cell Cardiol, 33 (2), 317-29, 2001.
  21. Fain, JN, Cowan, GS, Buffington, C, Andersen, RN, Pouncey, L, Bahouth, SW. Regulation of leptin release by troglitazone in human adipose tissue. Metabolism, 49 (11), 1485-90, 2000.
  22. Fain, JN, Leffler, CW, Bahouth, SW, Rice, AM, Rivkees, SA. Regulation of leptin release and lipolysis by PGE2 in rat adipose tissue. Prostaglandins Other Lipid Mediat, 62 (4), 343-50, 2000.
  23. Fain, JN, Leffler, CW, Bahouth, SW. Eicosanoids as endogenous regulators of leptin release and lipolysis by mouse adipose tissue in primary culture. J Lipid Res, 41 (10), 1689-94, 2000.
  24. Fain, JN, Bahouth, SW. Regulation of leptin release by mammalian adipose tissue. Biochem Biophys Res Commun, 274 (3), 571-5, 2000.
  25. Fain, JN, Cowan, GS, Buffington, C, Li, J, Pouncey, L, Bahouth, SW. Synergism between insulin and low concentrations of isoproterenol in the stimulation of leptin release by cultured human adipose tissue. Metabolism, 49 (6), 804-9, 2000.
  26. Fain, JN, Bahouth, SW. Regulation of lipolysis and leptin biosynthesis in rodent adipose tissue by growth hormone. Metabolism, 49 (2), 239-44, 2000.
  27. Bahouth, SW. Western blot detection of adrenergic receptors. Methods Mol Biol, 126, 301-14, 2000.
  28. Bahouth, SW. Development of antibodies to adrenergic receptors. Methods Mol Biol, 126, 281-99, 2000.
  29. Fain, JN, Ihle, JH, Bahouth, SW. Stimulation of lipolysis but not of leptin release by growth hormone is abolished in adipose tissue from Stat5a and b knockout mice. Biochem Biophys Res Commun, 263 (1), 201-5, 1999.
  30. Fain, JN, Bahouth, SW. Hormonal regulation of 18S RNA, leptin mRNA, and leptin release in adipocytes from hypothyroid rats. Metabolism, 47 (12), 1455-61, 1998.
  31. Fain, JN, Bahouth, SW. Effect of tri-iodothyronine on leptin release and leptin mRNA accumulation in rat adipose tissue. Biochem J, 332 ( Pt 2), 361-6, 1998.
  32. Fain, JN, Bahouth, SW. Stimulation of leptin release by actinomycin D in rat adipocytes. Biochem Pharmacol, 55 (8), 1309-14, 1998.
  33. Bahouth, SW, Beauchamp, MJ, Park, EA. Identification of a retinoic acid response domain involved in the activation of the beta 1-adrenergic receptor gene by retinoic acid in F9 teratocarcinoma cells. Biochem Pharmacol, 55 (2), 215-25, 1998.
  34. Bahouth, SW, Cui, X, Beauchamp, MJ, Park, EA. Thyroid hormone induces beta1-adrenergic receptor gene transcription through a direct repeat separated by five nucleotides. J Mol Cell Cardiol, 29 (12), 3223-37, 1997.
  35. Bahouth, SW, Cui, X, Beauchamp, MJ, Shimomura, H, George, ST, Park, EA. Promoter analysis of the rat beta1-adrenergic receptor gene identifies sequences involved in basal expression. Mol Pharmacol, 51 (4), 620-9, 1997.
  36. Fain, JN, Coronel, EC, Beauchamp, MJ, Bahouth, SW. Expression of leptin and beta 3-adrenergic receptors in rat adipose tissue in altered thyroid states. Biochem J, 322 ( Pt 1), 145-50, 1997.
  37. Fain, JN, Gokmen-Polar, Y, Bahouth, SW. Wortmannin converts insulin but not oxytocin from an antilipolytic to a lipolytic agent in the presence of forskolin. Metabolism, 46 (1), 62-6, 1997.
  38. Bahouth, SW, Gokmen-Polar, Y, Coronel, EC, Fain, JN. Enhanced desensitization and phosphorylation of the beta 1-adrenergic receptor in rat adipocytes by peroxovanadate. Mol Pharmacol, 49 (6), 1049-57, 1996.
  39. Gokmen-Polar, Y, Coronel, EC, Bahouth, SW, Fain, JN. Insulin sensitizes beta-agonist and forskolin-stimulated lipolysis to inhibition by 2',5'-dideoxyadenosine. Am J Physiol, 270 (2 Pt 1), C562-9, 1996.
  40. Bahouth, SW, Park, EA, Beauchamp, M, Cui, X, Malbon, CC. Identification of a glucocorticoid repressor domain in the rat beta 1-adrenergic receptor gene. Recept Signal Transduct, 6 (3-4), 141-9, 1996.
  41. Park, EA, Jerden, DC, Bahouth, SW. Regulation of phosphoenolpyruvate carboxykinase gene transcription by thyroid hormone involves two distinct binding sites in the promoter. Biochem J, 309 ( Pt 3), 913-9, 1995.
  42. Bahouth, SW. Thyroid hormone regulation of transmembrane signalling in neonatal rat ventricular myocytes by selective alteration of the expression and coupling of G-protein alpha-subunits. Biochem J, 307 ( Pt 3), 831-41, 1995.
  43. Kang, ES, Betts, D, Fain, JN, Bahouth, SW, Myers, LK. Chronic exposure of rat fat cells to insulin enhances lipolysis and activation of partially purified hormone-sensitive lipase. Diabetes, 42 (10), 1415-24, 1993.
  44. Bahouth, SW. Effects of chemical and surgical sympathectomy on expression of beta-adrenergic receptors and guanine nucleotide-binding proteins in rat submandibular glands. Mol Pharmacol, 42 (6), 971-81, 1992.
  45. Bahouth, SW, Lopez, S. Insulin desensitized beta 1-adrenergic receptor-mediated stimulation of adenylyl cyclase in SK-N-MC cells. Life Sci, 51 (26), PL271-6, 1992.
  46. Bahouth, SW, Wang, HY, Malbon, CC. Immunological approaches for probing receptor structure and function. Trends Pharmacol Sci, 12 (9), 338-43, 1991.
  47. Bahouth, SW. Thyroid hormones transcriptionally regulate the beta 1-adrenergic receptor gene in cultured ventricular myocytes. J Biol Chem, 266 (24), 15863-9, 1991.