Professor Arthur Conigrave
G08 - Biochemistry Building
The University of Sydney NSW 2006 Australia |
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Proteins are essential structural and functional components of our bodies. It is impossible to imagine human life without them. Amino acids are the building blocks of proteins and our bodies need a regular supply of amino acids to replace proteins that are "worn out". For this reason, the cells of our bodies bristle with sensing mechanisms that detect variations in amino acid levels. Reductions in amino acid levels in the brain, for example, provide a powerful stimulus to appetite. The presence of amino acids in the gut, on the other hand, promotes intestinal digestion and absorption and elevated levels in blood trigger the release of hormones that coordinate growth and the uptake of amino acids by cells for protein synthesis and tissue building. Our laboratory is concerned with the molecules that sense changes in amino acid levels and currently focusses on a subgroup of the G-protein coupled receptor superfamily ("class 3") that includes a number of broad-spectrum amino acid sensors involved in triggering both gut digestive responses as well as hormonal regulatory responses.
Current national competitive grants
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2009 |
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Understanding the pharmacoregulation of the extracellular calcium sending receptor |
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| NHMRC Research Project Shared Support | $285,000 over 3 years |
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2008 |
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Molecular mechanism and novel activators of amino acid and calcium-sensing class 3 G-protein coupled receptors |
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| NHMRC Project Grant | $498,750 over 3 years |
2010
- Ooi, L, Zheng, Y, Zhou, H, Trivedi, T, Conigrave, A, Seibel, M, Dunstan, C. Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis. Bone. 2010; :
- Gosby, A, Campbell, C, Badaloo, A, Soares-Wynter, S, Antonelli, M, Hall, R, Martinez-Cordero, C, Jebb, S, Brand-Miller, J, Caterson, I, Conigrave, A, Forrester, T, Raubenheimer, D, Simpson, S. Design and testing of foods differing in protein to energy ratios. Appetite. 2010; :
- Clissold, F, Tedder, B, Conigrave, A, Simpson, S. The gastrointestinal tract as a nutrient-balancing organ. Proceedings. Biological sciences / The Royal Society. 2010; 277:1751-9
- Conigrave, A, Hampson, D. Broad-spectrum amino acid-sensing class C G-protein coupled receptors: Molecular mechanisms, physiological significance and options for drug development. Pharmacology & therapeutics. 2010; :
- Hannan, F, Nesbit, M, Turner, J, Stacey, J, Cianferotti, L, Christie, P, Conigrave, A, Whyte, M, Thakker, R. Comparison of human chromosome 19q13 and syntenic region on mouse chromosome 7 reveals absence, in man, of 11.6 Mb containing four mouse calcium-sensing receptor-related sequences: relevance to familial benign hypocalciuric hypercalcaemia type 3. European journal of human genetics : EJHG. 2010; 18:442-7
- Khan, M, Conigrave, A. Mechanisms of multimodal sensing by extracellular Ca(2+)-sensing receptors: a domain-based survey of requirements for binding and signalling. British Journal of Pharmacology. 2010; 159:1039-1050
2009
- Szekely, D, Brennan, S, Mun, H, Conigrave, A, Kuchel, P. Effectors of the frequency of calcium oscillations in HEK-293 cells: wavelet analysis and a computer model. European biophysics journal : EBJ. 2009; 39:149-65
- Mun, H, Brennan, S, Delbridge, L, Wilkinson, M, Brown, E, Conigrave, A. Adenomatous human parathyroid cells exhibit impaired sensitivity to L-amino acids. The Journal of clinical endocrinology and metabolism. 2009; 94:3567-74
- Brennan, T, Rybchyn, M, Green, W, Atwa, S, Conigrave, A, Mason, R. Osteoblasts play key roles in the mechanisms of action of strontium ranelate. British journal of pharmacology. 2009; 157:1291-300
- Brennan, S, Conigrave, A. Regulation of cellular signal transduction pathways by the extracellular calcium-sensing receptor. Current pharmaceutical biotechnology. 2009; 10:270-81
2008
- Au, A, McDonald, K, Gill, A, Sywak, M, Diamond, T, Conigrave, A, Clifton-Bligh, R. PTH Mutation with Primary Hyperparathyroidism and Undetectable Intact PTH. The New England journal of medicine. 2008; 359:1184-1186
- Lu, M, Forsberg, L, Höög, A, Juhlin, C, Vukojević, V, Larsson, C, Conigrave, A, Delbridge, L, Gill, A, Bark, C, Farnebo, L, Bränström, R. Heterogeneous expression of SNARE proteins SNAP-23, SNAP-25, Syntaxin1 and VAMP in human parathyroid tissue. Molecular and cellular endocrinology. 2008; 287:72-80
- Conigrave, A, Brown, E, Rizzoli, R. Dietary Protein and Bone Health: Roles of Amino Acid-Sensing Receptors in the Control of Calcium Metabolism and Bone Homeostasis. Annual review of nutrition. 2008; 28:131-55
2007
- Conigrave, A, Mun, H, Brennan, S. Physiological significance of L-amino acid sensing by extracellular Ca(2+)-sensing receptors. Biochemical Society transactions. 2007; 35:1195-8
- Conigrave, A, Mun, H, Lok, H. Aromatic L-amino acids activate the calcium-sensing receptor. The Journal of nutrition. 2007; 137:1524S-1527S; discussion 1548S
- Lee, H, Mun, H, Lewis, N, Crouch, M, Culverston, E, Mason, R, Conigrave, A. Allosteric activation of the extracellular Ca2+-sensing receptor by L-amino acids enhances ERK1/2 phosphorylation. The Biochemical journal. 2007; 404:141-149
- Brennan, T, Rybchyn, M, Conigrave, A, Mason, R. Strontium ranelate effects on bone formation and bone resorption: an in vitro in human osteoblasts. OSTEOPOROSIS INTERNATIONAL. 2007; 18:S166-S167
- Brennan, T, Rybchyn, M, Halbout, P, Conigrave, A, Mason, R. Strontium ranelate effects in human osteoblasts support its uncoupling effect on bone formation and bone resorption. CALCIFIED TISSUE INTERNATIONAL. 2007; 80:S72-S73
2006
- Conigrave, A, Hampson, D. Broad-spectrum l-amino acid sensing by class 3 G-protein-coupled receptors. Trends in endocrinology and metabolism: TEM. 2006; 17:398-407
- Conigrave, A, Brown, E. Taste Receptors in the Gastrointestinal Tract II. L-Amino acid sensing by calcium-sensing receptors: implications for GI physiology. American journal of physiology. Gastrointestinal and liver physiology. 2006; 291:G753-61
2005
- Mun, H, Conigrave, A, Wilkinson, M, Delbridge, L. Surgery for hyperparathyroidism: does morphology or function matter most?. Surgery. 2005; 138:1111-20; discussion 1120
- Mun, H, Culverston, E, Franks, A, Collyer, C, Clifton-Bligh, R, Conigrave, A. A double mutation in the extracellular Ca2+-sensing receptor's venus flytrap domain that selectively disables L-amino acid sensing. The Journal of biological chemistry. 2005; 280:29067-72
2004
- Mun, H, Franks, A, Culverston, E, Krapcho, K, Nemeth, E, Conigrave, A. The Venus Fly Trap domain of the extracellular Ca2+ -sensing receptor is required for L-amino acid sensing. The Journal of biological chemistry. 2004; 279:51739-44
- Conigrave, A, Mun, H, Delbridge, L, Quinn, S, Wilkinson, M, Brown, E. L-amino acids regulate parathyroid hormone secretion. The Journal of biological chemistry. 2004; 279:38151-9
- Shemon, A, Sluyter, R, Conigrave, A, Wiley, J. Chelerythrine and other benzophenanthridine alkaloids block the human P2X7 receptor. British journal of pharmacology. 2004; 142:1015-9
- Conigrave, A, Lok, H. Activation of renal calcium and water excretion by novel physiological and pharmacological activators of the calcium-sensing receptor. Clinical and experimental pharmacology & physiology. 2004; 31:368-71
2003
- Conigrave, A, Franks, A. Allosteric activation of plasma membrane receptors--physiological implications and structural origins. Progress in biophysics and molecular biology. 2003; 81:219-40
- Rae, C, Hare, N, Bubb, W, McEwan, S, Bröer, A, McQuillan, J, Balcar, V, Conigrave, A, Bröer, S. Inhibition of glutamine transport depletes glutamate and GABA neurotransmitter pools: further evidence for metabolic compartmentation. Journal of neurochemistry. 2003; 85:503-14
- Tan, Y, Cardinal, J, Franks, A, Mun, H, Lewis, N, Harris, L, Prins, J, Conigrave, A. Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor. The Journal of clinical endocrinology and metabolism. 2003; 88:605-10
2002
- Conigrave, A, Franks, A, Brown, E, Quinn, S. L-amino acid sensing by the calcium-sensing receptor: a general mechanism for coupling protein and calcium metabolism?. European journal of clinical nutrition. 2002; 56:1072-80
- Zhang, Z, Qiu, W, Quinn, S, Conigrave, A, Brown, E, Bai, M. Three adjacent serines in the extracellular domains of the CaR are required for L-amino acid-mediated potentiation of receptor function. The Journal of biological chemistry. 2002; 277:33727-35
- Bradbury, R, Cropley, J, Kifor, O, Lovicu, F, de Iongh, R, Kable, E, Brown, E, Seely, E, Peat, B, Conigrave, A. Localization of the extracellular Ca(2+)-sensing receptor in the human placenta. Placenta. 2002; 23:192-200
2001
- Conigrave, A, Fernando, K, Gu, B, Tasevski, V, Zhang, W, Luttrell, B, Wiley, J. P2Y11 receptor expression by human lymphocytes: evidence for two cAMP-linked purinoceptors. European Journal of Pharmacology. 2001; 142:2147-2150
2000
- Conigrave, A, van der Weyden, L, Holt, L, Jiang, L, Wilson, P, Christopherson, R, Morris, M. Extracellular ATP-dependent suppression of proliferation and induction of differentiation of human HL-60 leukemia cells by distinct mechanisms. Biochemical pharmacology. 2000; 60:1585-91
- van der Weyden, L, Rakyan, V, Luttrell, B, Morris, M, Conigrave, A. Extracellular ATP couples to cAMP generation and granulocytic differentiation in human NB4 promyelocytic leukaemia cells. Immunology and cell biology. 2000; 78:467-73
- Conigrave, A, Quinn, S, Brown, E. Cooperative multi-modal sensing and therapeutic implications of the extracellular Ca(2+) sensing receptor. Trends in pharmacological sciences. 2000; 21:401-7
- van der Weyden, L, Conigrave, A, Morris, M. Signal transduction and white cell maturation via extracellular ATP and the P2Y11 receptor. Immunology and cell biology. 2000; 78:369-74
- Conigrave, A, Quinn, S, Brown, E. L-amino acid sensing by the extracellular Ca2+-sensing receptor. Proceedings of the National Academy of Sciences of the United States of America. 2000; 97:4814-9
- van der Weyden, L, Adams, D, Luttrell, B, Conigrave, A, Morris, M. Pharmacological characterisation of the P2Y11 receptor in stably transfected haematological cell lines. Mollecular and Cellular Biochemistry. 2000; 213(1/2):75-81
