John H. Exton, M.B.Ch.B, Ph.D., M.D.

Professor

john.exton@vanderbilt.edu
Faculty Appointments
Professor of Molecular Physiology and Biophysics Professor of Pharmacology
Education
M.D., Biochemistry, University of Otago, Dunedin, New ZealandPh.D., Biochemistry, University of Otago, Dunedin, New ZealandM.B.Ch.B, Medicine, University of New Zealand, Dunedin, New ZealandB.Med.Sc., Biochemistry, University of New Zealand, Dunedin, New Zealand
Office Address
831B Light Hall
TN 0295
Research Description
Many hormones, neurotransmitters and growth factors produce their physiological actions by stimulating the breakdown of certain phospholipids in their target cells. This leads to an increase in the concentration of Ca2+ ions and changes in lipid messenger molecules that are responsible for the physiological effects observed. We are studying the phospholipase isozymes that are specifically involved in agonist-stimulated phospholipid breakdown and also the G proteins, protein kinases and other factors involved in their regulation. The structural elements required for catalysis and the domains and mechanisms of interaction of the phopholipases and their regulatory proteins are being defined. We are also exploring the molecular mechanisms by which hormones and growth factors stimulate phospholipid breakdown in intact cells, in particular, those mechanisms involving large and small G proteins and protein tyrosine and serine-threonine kinases. We are also examining the roles played by some of the products of phospholipid breakdown (phosphatidic acid and diacylglycerol) in generating physiological responses. The approaches involve the generation of mutant forms of the enzymes and regulatory proteins that are constitutively active or function as dominant negative forms, and the use of cells and animals in which the proteins are selectively depleted. This information is aimed at helping us understand how some of the important physiological reponses to hormones, neurotransmitters and growth factors are generated.

Research Keywords
Mechanisms of cell signaling
Publications
Couvillon AD, Exton JH. Role of heterotrimeric G-proteins in lysophosphatidic acid-mediated neurite retraction by RhoA-dependent and -independent mechanisms in N1E-115 cells. Cell. Signal [print-electronic]. 2006 May; 18(5): 715-28. PMID: 16122906, PII: S0898-6568(05)00157-9, DOI: 10.1016/j.cellsig.2005.06.012, ISSN: 0898-6568.

Hu P, Han Z, Couvillon AD, Kaufman RJ, Exton JH. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol. Cell. Biol. 2006 Apr; 26(8): 3071-84. PMID: 16581782, PMCID: PMC1446932, PII: 26/8/3071, DOI: 10.1128/MCB.26.8.3071-3084.2006, ISSN: 0270-7306.

Henage LG, Exton JH, Brown HA. Kinetic analysis of a mammalian phospholipase D: allosteric modulation by monomeric GTPases, protein kinase C, and polyphosphoinositides. J. Biol. Chem [print-electronic]. 2006 Feb 2/10/2006; 281(6): 3408-17. PMID: 16339153, PMCID: PMC3800466, PII: M508800200, DOI: 10.1074/jbc.M508800200, ISSN: 0021-9258.

Kook S, Exton JH. Identification of interaction sites of protein kinase Calpha on phospholipase D1. Cell. Signal. 2005 Nov; 17(11): 1423-32. PMID: 15951158, PII: S0898-6568(05)00053-7, DOI: 10.1016/j.cellsig.2005.03.003, ISSN: 0898-6568.

Chen JS, Exton JH. Sites on phospholipase D2 phosphorylated by PKCalpha. Biochem. Biophys. Res. Commun. 2005 Aug 8/12/2005; 333(4): 1322-6. PMID: 15979581, PII: S0006-291X(05)01243-X, DOI: 10.1016/j.bbrc.2005.06.048, ISSN: 0006-291X.

Hu T, Exton JH. A point mutation at phenylalanine 663 abolishes protein kinase C alpha's ability to translocate to the perinuclear region and activate phospholipase D1. Biochem. Biophys. Res. Commun. 2005 Aug 8/5/2005; 333(3): 750-3. PMID: 15963950, PII: S0006-291X(05)01150-2, DOI: 10.1016/j.bbrc.2005.05.184, ISSN: 0006-291X.

Ho WT, Xie Z, Zhao ZJ, Exton JH. Tyrosine phosphorylation of phospholipase D1 by v-Src does not per se result in activation. Cell. Signal. 2005 Jun; 17(6): 691-9. PMID: 15722193, PII: S0898-6568(04)00229-3, DOI: 10.1016/j.cellsig.2004.10.007, ISSN: 0898-6568.

Hiroyama M, Exton JH. Localization and regulation of phospholipase D2 by ARF6. J. Cell. Biochem. 2005 May 5/1/2005; 95(1): 149-64. PMID: 15759270, DOI: 10.1002/jcb.20351, ISSN: 0730-2312.

Hu T, Exton JH. 1-Butanol interferes with phospholipase D1 and protein kinase Calpha association and inhibits phospholipase D1 basal activity. Biochem. Biophys. Res. Commun. 2005 Feb 2/25/2005; 327(4): 1047-51. PMID: 15652502, PII: S0006-291X(04)02882-7, DOI: 10.1016/j.bbrc.2004.12.117, ISSN: 0006-291X.

Buchanan FG, McReynolds M, Couvillon A, Kam Y, Holla VR, Dubois RN, Exton JH. Requirement of phospholipase D1 activity in H-RasV12-induced transformation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2005 Feb 2/1/2005; 102(5): 1638-42. PMID: 15668389, PMCID: PMC547811, PII: 0406698102, DOI: 10.1073/pnas.0406698102, ISSN: 0027-8424.

Hiroyama M, Exton JH. Studies of the roles of ADP-ribosylation factors and phospholipase D in phorbol ester-induced membrane ruffling. J. Cell. Physiol. 2005 Feb; 202(2): 608-22. PMID: 15389577, DOI: 10.1002/jcp.20156, ISSN: 0021-9541.

Hu T, Exton JH. Protein kinase Calpha translocates to the perinuclear region to activate phospholipase D1. J. Biol. Chem [print-electronic]. 2004 Aug 8/20/2004; 279(34): 35702-8. PMID: 15187091, PII: M402372200, DOI: 10.1074/jbc.M402372200, ISSN: 0021-9258.

Chen JS, Exton JH. Regulation of phospholipase D2 activity by protein kinase C alpha. J. Biol. Chem [print-electronic]. 2004 May 5/21/2004; 279(21): 22076-83. PMID: 15031293, PII: M311033200, DOI: 10.1074/jbc.M311033200, ISSN: 0021-9258.

Kam Y, Exton JH. Role of phospholipase D in the activation of protein kinase D by lysophosphatidic acid. Biochem. Biophys. Res. Commun. 2004 Feb 2/27/2004; 315(1): 139-43. PMID: 15013437, PII: S0006291X04000622, DOI: 10.1016/j.bbrc.2004.01.034, ISSN: 0006-291X.

Kam Y, Exton JH. Role of phospholipase D1 in the regulation of mTOR activity by lysophosphatidic acid. FASEB J. 2004 Feb; 18(2): 311-9. PMID: 14769825, PII: 18/2/311, DOI: 10.1096/fj.03-0731com, ISSN: 1530-6860.

Ho WT, Exton JH, Williger BT. Arfaptin 1 inhibits ADP-ribosylation factor-dependent matrix metalloproteinase-9 secretion induced by phorbol ester in HT 1080 fibrosarcoma cells. FEBS Lett. 2003 Feb 2/27/2003; 537(1-3): 91-5. PMID: 12606037, PII: S001457930300098X, ISSN: 0014-5793.

Hu T, Exton JH. Mechanisms of regulation of phospholipase D1 by protein kinase Calpha. J. Biol. Chem [print-electronic]. 2003 Jan 1/24/2003; 278(4): 2348-55. PMID: 12431982, PII: M210093200, DOI: 10.1074/jbc.M210093200, ISSN: 0021-9258.

Exton JH. Regulation of phospholipase D. FEBS Lett. 2002 Oct 10/30/2002; 531(1): 58-61. PMID: 12401203, PII: S0014579302034051, ISSN: 0014-5793.

Xie Z, Ho WT, Spellman R, Cai S, Exton JH. Mechanisms of regulation of phospholipase D1 and D2 by the heterotrimeric G proteins G13 and Gq. J. Biol. Chem [print-electronic]. 2002 Apr 4/5/2002; 277(14): 11979-86. PMID: 11812783, PII: M109751200, DOI: 10.1074/jbc.M109751200, ISSN: 0021-9258.

Xie Z, Ho WT, Exton JH. Functional implications of post-translational modifications of phospholipases D1 and D2. Biochim. Biophys. Acta. 2002 Jan 1/30/2002; 1580(1): 9-21. PMID: 11923096, PII: S1388198101001688, ISSN: 0006-3002.

Kam Y, Exton JH. Dimerization of phospholipase d isozymes. Biochem. Biophys. Res. Commun. 2002 Jan 1/11/2002; 290(1): 375-80. PMID: 11779179, PII: S0006291X01961467, DOI: 10.1006/bbrc.2001.6146, ISSN: 0006-291X.

Exton JH. Phospholipase D-structure, regulation and function. Rev. Physiol. Biochem. Pharmacol. 2002; 144: 1-94. PMID: 11987824, ISSN: 0303-4240.

Xie Z, Kim HK, Exton JH. Expression and characterization of rat brain phospholipase D. Meth. Enzymol. 2002; 345: 255-64. PMID: 11665609, ISSN: 0076-6879.

Xie, Z., Ho, W.-T., Spellmlan, R., Cai, S. and Exton, J.H. Mechanisms of regulation of phospholipase D1 and D2 by the heterotrimeric G proteins G(13) and G(q). J. Biol. Chem. 2002; 277: 11979-86.

Shin OH, Couvillon AD, Exton JH. Arfophilin is a common target of both class II and class III ADP-ribosylation factors. Biochemistry. 2001 Sep 9/11/2001; 40(36): 10846-52. PMID: 11535061, PII: bi0107391, ISSN: 0006-2960.

Shin OH, Exton JH. Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1. Biochem. Biophys. Res. Commun. 2001 Aug 8/3/2001; 285(5): 1267-73. PMID: 11478794, PII: S0006-291X(01)95330-6, DOI: 10.1006/bbrc.2001.5330, ISSN: 0006-291X.

Kam Y, Exton JH. Phospholipase D activity is required for actin stress fiber formation in fibroblasts. Mol. Cell. Biol. 2001 Jun; 21(12): 4055-66. PMID: 11359912, PMCID: PMC87067, DOI: 10.1128/MCB.21.12.4055-4066.2001, ISSN: 0270-7306.

Cai S, Exton JH. Determination of interaction sites of phospholipase D1 for RhoA. Biochem. J. 2001 May 5/1/2001; 355(Pt 3): 779-85. PMID: 11311142, PMCID: PMC1221795, ISSN: 0264-6021.

Xie Z, Ho WT, Exton JH. Requirements and effects of palmitoylation of rat PLD1. J. Biol. Chem [print-electronic]. 2001 Mar 3/23/2001; 276(12): 9383-91. PMID: 11121416, PII: M009425200, DOI: 10.1074/jbc.M009425200, ISSN: 0021-9258.

Xie, Z., Ho, W.-T. and Exton, J.H. Requirements and effects of palmitoylation of rat PLD1. J. Biol. Chem. 2001; 276: 9383-91.

Kam, Y. and Exton, J.H. Phospholipase D activity as required for actin stress fiber formation in fibroblasts. Mol. Cell. Biol. 2001; 21: 4055-66.

Xie Z, Ho WT, Exton JH. Conserved amino acids at the C-terminus of rat phospholipase D1 are essential for enzymatic activity. Eur. J. Biochem. 2000 Dec; 267(24): 7138-46. PMID: 11106425, PII: ejb1816, ISSN: 0014-2956.

Jin S, Exton JH. Activation of RhoA by association of Galpha(13) with Dbl. Biochem. Biophys. Res. Commun. 2000 Nov 11/2/2000; 277(3): 718-21. PMID: 11062019, PII: S0006-291X(00)93744-6, DOI: 10.1006/bbrc.2000.3744, ISSN: 0006-291X.

Xie Z, Ho WT, Exton JH. Association of the N- and C-terminal domains of phospholipase D. Contribution of the conserved HKD motifs to the interaction and the requirement of the association for Ser/Thr phosphorylation of the enzyme. J. Biol. Chem. 2000 Aug 8/11/2000; 275(32): 24962-9. PMID: 10825182, PII: M909745199, DOI: 10.1074/jbc.M909745199, ISSN: 0021-9258.

Exton JH. Phospholipase D. Ann. N. Y. Acad. Sci. 2000 Apr; 905: 61-8. PMID: 10818442, ISSN: 0077-8923.

Buchanan FG, Elliot CM, Gibbs M, Exton JH. Translocation of the Rac1 guanine nucleotide exchange factor Tiam1 induced by platelet-derived growth factor and lysophosphatidic acid. J. Biol. Chem. 2000 Mar 3/31/2000; 275(13): 9742-8. PMID: 10734127, ISSN: 0021-9258.

Hess JA, Buchanan FG, Ryder S, Exton JH. Altered activation of phospholipase D by lysophosphatidic acid and endothelin-1 in mouse embryo fibroblasts lacking phospholipase C-gamma1. Cell. Signal. 2000 Jan; 12(1): 37-45. PMID: 10676846, PII: S0898-6568(99)00075-3, ISSN: 0898-6568.

Buchanan, F.G., Elliott, C.M., Gibbs M. and Exton, J.H. Translocation of the Rac1 guanine nucleotide exchange factor and lysophosphatidic acid. J. Biol. Chem. 2000; 275: 9742-8.

Shin OH, Ross AH, Mihai I, Exton JH. Identification of arfophilin, a target protein for GTP-bound class II ADP-ribosylation factors. J. Biol. Chem. 1999 Dec 12/17/1999; 274(51): 36609-15. PMID: 10593962, ISSN: 0021-9258.

Exton JH. Regulation of phospholipase D. Biochim. Biophys. Acta. 1999 Jul 7/30/1999; 1439(2): 121-33. PMID: 10425390, PII: S1388-1981(99)00089-X, ISSN: 0006-3002.

Williger BT, Provost JJ, Ho WT, Milstine J, Exton JH. Arfaptin 1 forms a complex with ADP-ribosylation factor and inhibits phospholipase D. FEBS Lett. 1999 Jul 7/2/1999; 454(1-2): 85-9. PMID: 10413101, PII: S0014-5793(99)00771-1, ISSN: 0014-5793.

Fleming IN, Elliott CM, Buchanan FG, Downes CP, Exton JH. Ca2+/calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation. J. Biol. Chem. 1999 Apr 4/30/1999; 274(18): 12753-8. PMID: 10212259, ISSN: 0021-9258.

Williger BT, Ostermann J, Exton JH. Arfaptin 1, an ARF-binding protein, inhibits phospholipase D and endoplasmic reticulum/Golgi protein transport. FEBS Lett. 1999 Jan 1/25/1999; 443(2): 197-200. PMID: 9989604, PII: S0014-5793(98)01707-4, ISSN: 0014-5793.

Williger BT, Ho WT, Exton JH. Phospholipase D mediates matrix metalloproteinase-9 secretion in phorbol ester-stimulated human fibrosarcoma cells. J. Biol. Chem. 1999 Jan 1/8/1999; 274(2): 735-8. PMID: 9873009, ISSN: 0021-9258.

Fleming, I.N., Elliott, C.M., Buchanan, F.G. and Exton, J.H. Ca2+calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation. J. Biol. Chem. 1999; 274: 12753-8.

Xie Z, Ho WT, Exton JH. Association of N- and C-terminal domains of phospholipase D is required for catalytic activity. J. Biol. Chem. 1998 Dec 12/25/1998; 273(52): 34679-82. PMID: 9856987, ISSN: 0021-9258.

Exton JH. Phospholipase D. Biochim. Biophys. Acta. 1998 Dec 12/8/1998; 1436(1-2): 105-15. PMID: 9838067, PII: S0005-2760(98)00124-6, ISSN: 0006-3002.

Min DS, Kim EG, Exton JH. Involvement of tyrosine phosphorylation and protein kinase C in the activation of phospholipase D by H2O2 in Swiss 3T3 fibroblasts. J. Biol. Chem. 1998 Nov 11/6/1998; 273(45): 29986-94. PMID: 9792719, ISSN: 0021-9258.

Guillemain I, Exton JH. Role of rho proteins in agonist regulation of phospholipase D in HL-60 cells. Biochim. Biophys. Acta. 1998 Oct 10/21/1998; 1405(1-3): 161-70. PMID: 9784628, PII: S0167-4889(98)00107-4, ISSN: 0006-3002.

Hess JA, Ji QS, Carpenter G, Exton JH. Analysis of platelet-derived growth factor-induced phospholipase D activation in mouse embryo fibroblasts lacking phospholipase C-gamma1. J. Biol. Chem. 1998 Aug 8/7/1998; 273(32): 20517-24. PMID: 9685408, ISSN: 0021-9258.

Exton JH. Small GTPases minireview series. J. Biol. Chem. 1998 Aug 8/7/1998; 273(32): 19923. PMID: 9685324, ISSN: 0021-9258.

Min DS, Exton JH. Phospholipase D is associated in a phorbol ester-dependent manner with protein kinase C-alpha and with a 220-kDa protein which is phosphorylated on serine and threonine. Biochem. Biophys. Res. Commun. 1998 Jul 7/30/1998; 248(3): 533-7. PMID: 9703960, PII: S0006-291X(98)98990-2, DOI: 10.1006/bbrc.1998.8990, ISSN: 0006-291X.

Fleming IN, Elliott CM, Exton JH. Phospholipase C-gamma, protein kinase C and Ca2+/calmodulin-dependent protein kinase II are involved in platelet-derived growth factor-induced phosphorylation of Tiam1. FEBS Lett. 1998 Jun 6/16/1998; 429(3): 229-33. PMID: 9662423, PII: S0014-5793(98)00566-3, ISSN: 0014-5793.

Bae CD, Min DS, Fleming IN, Exton JH. Determination of interaction sites on the small G protein RhoA for phospholipase D. J. Biol. Chem. 1998 May 5/8/1998; 273(19): 11596-604. PMID: 9565577, ISSN: 0021-9258.

Min DS, Park SK, Exton JH. Characterization of a rat brain phospholipase D isozyme. J. Biol. Chem. 1998 Mar 3/20/1998; 273(12): 7044-51. PMID: 9507013, ISSN: 0021-9258.

Park SK, Min DS, Exton JH. Definition of the protein kinase C interaction site of phospholipase D. Biochem. Biophys. Res. Commun. 1998 Mar 3/17/1998; 244(2): 364-7. PMID: 9514932, PII: S0006-291X(98)98275-4, DOI: 10.1006/bbrc.1998.8275, ISSN: 0006-291X.

Plonk SG, Park SK, Exton JH. The alpha-subunit of the heterotrimeric G protein G13 activates a phospholipase D isozyme by a pathway requiring Rho family GTPases. J. Biol. Chem. 1998 Feb 2/27/1998; 273(9): 4823-6. PMID: 9478920, ISSN: 0021-9258.

Plonk, S. G., Park, S. -K. and Exton, J. H. The a-subunit of the heterotrimeric G protein G13 activates a phospholipase D isozyme by a pathway requiring Rho-family GTPases. J. Biol. Chem. 1998; 273: 4823-36.

Xie, Z., Ho, W.-T. and Exton, J.H. Association of N- and C-terminal domains of phospholipase D is required for catalytic activity. J. Biol. Chem. 1998; 273: 34679-82.

Min, D.S., Park, S.-K. and Exton, J.H. Characterization of a rat brain phospholipase D isozyme. J. Biol. Chem. 1998; 273: 7044-51.

Bae, C.D., Min, D.S., Fleming, I.N. and Exton, J.H. Determination of interaction sites on the small G protein RhoA for phospholipase D. J. Biol. Chem. 1998; 273: 11596-604.

Tsai, S-C., Adamik, R., Hong, J-X., Moss, J., Vaughan, M., Kanoh, H. and Exton, J.H. Effects of arfaptin 1 on guanine nucleotide-dependent activation of phospholipase D and cholera toxin by ARF. J. Biol. Chem. 1998; 273: 20697-701.

Min, D.S., Kim, E.-G. and Exton, J.H. Involvement of tyrosine phosphorylation and protein kinase C in the activation of phospholipase D by H2O2 in Swiss 3T3 fibroblasts. J. Biol. Chem. 1998; 273: 29986-94.

Fleming IN, Elliott CM, Collard JG, Exton JH. Lysophosphatidic acid induces threonine phosphorylation of Tiam1 in Swiss 3T3 fibroblasts via activation of protein kinase C. J. Biol. Chem. 1997 Dec 12/26/1997; 272(52): 33105-10. PMID: 9407095, ISSN: 0021-9258.

Park SK, Provost JJ, Bae CD, Ho WT, Exton JH. Cloning and characterization of phospholipase D from rat brain. J. Biol. Chem. 1997 Nov 11/14/1997; 272(46): 29263-71. PMID: 9361006, ISSN: 0021-9258.

Guillemain I, Exton JH. Effects of brefeldin A on phosphatidylcholine phospholipase D and inositolphospholipid metabolism in HL-60 cells. Eur. J. Biochem. 1997 Nov 11/1/1997; 249(3): 812-9. PMID: 9395331, ISSN: 0014-2956.

Exton JH. New developments in phospholipase D. J. Biol. Chem. 1997 Jun 6/20/1997; 272(25): 15579-82. PMID: 9188441, ISSN: 0021-9258.

Yeo EJ, Provost JJ, Exton JH. Dissociation of tyrosine phosphorylation and activation of phosphoinositide phospholipase C induced by the protein kinase C inhibitor Ro-31-8220 in Swiss 3T3 cells treated with platelet-derived growth factor. Biochim. Biophys. Acta. 1997 May 5/27/1997; 1356(3): 308-20. PMID: 9194574, PII: S0167-4889(97)00006-2, ISSN: 0006-3002.

Exton JH. Phospholipase D: enzymology, mechanisms of regulation, and function. Physiol. Rev. 1997 Apr; 77(2): 303-20. PMID: 9114816, ISSN: 0031-9333.

Kanoh H, Williger BT, Exton JH. Arfaptin 1, a putative cytosolic target protein of ADP-ribosylation factor, is recruited to Golgi membranes. J. Biol. Chem. 1997 Feb 2/28/1997; 272(9): 5421-9. PMID: 9038142, ISSN: 0021-9258.

Hess JA, Ross AH, Qiu RG, Symons M, Exton JH. Role of Rho family proteins in phospholipase D activation by growth factors. J. Biol. Chem. 1997 Jan 1/17/1997; 272(3): 1615-20. PMID: 8999836, ISSN: 0021-9258.

Exton JH. Cell signalling through guanine-nucleotide-binding regulatory proteins (G proteins) and phospholipases. Eur. J. Biochem. 1997 Jan 1/15/1997; 243(1-2): 10-20. PMID: 9030716, ISSN: 0014-2956.

Kanoh, H. and Exton, J.H. Arfaptin 1, a putative cytosolic target protein of ADP-ribosylation factor, is recruited to Golgi membranes. J. Biol. Chem. 1997; 272: 5421-9.

Hess, J.A., Ross, A.H., Qui, R.-G., Symons, M. and Exton, J.H. Role of Rho family proteins in phospholipase D activation by growth factors. J. Biol. Chem. 1997; 272: 1615-20.

Kanoh, H. and Exton, J.H. Arfaptin 1, a putative cytosolic target protein of ADP-ribosylation factor, is recruited to Golgi membranes. 272. 1997; 5421-5429: J. Biol. Chem.

Park, S.-K., Provost, J.J., Bae, C.D., Ho, W.-T. and Exton, J.H. Cloning and characterization of phospholipase D from rat brain. J. Biol. Chem. 1997; 272: 29263-71.

Fleming, I.N., Elliott, C.M., Collard, J.G. and Exton, J.H. Lysophosphatidic acid induces phosphorylation of Tiam1 in Swiss 3T3 fibroblasts via activation of protein kinase C. J. Biol. Chem. 1997; 272: 33105-10.

Fleming IN, Elliott CM, Exton JH. Differential translocation of rho family GTPases by lysophosphatidic acid, endothelin-1, and platelet-derived growth factor. J. Biol. Chem. 1996 Dec 12/20/1996; 271(51): 33067-73. PMID: 8955154, ISSN: 0021-9258.

Provost JJ, Fudge J, Israelit S, Siddiqi AR, Exton JH. Tissue-specific distribution and subcellular distribution of phospholipase D in rat: evidence for distinct RhoA- and ADP-ribosylation factor (ARF)-regulated isoenzymes. Biochem. J. 1996 Oct 10/1/1996; 319 ( Pt 1): 285-91. PMID: 8870680, PMCID: PMC1217766, ISSN: 0264-6021.

Malcolm KC, Sable CL, Elliott CM, Exton JH. Enhanced phospholipase D activity and altered morphology in RhoA-overexpressing RAT1 fibroblasts. Biochem. Biophys. Res. Commun. 1996 Aug 8/14/1996; 225(2): 514-9. PMID: 8753793, PII: S0006-291X(96)91204-8, DOI: 10.1006/bbrc.1996.1204, ISSN: 0006-291X.

Pete MJ, Exton JH. Purification of a lysophospholipase from bovine brain that selectively deacylates arachidonoyl-substituted lysophosphatidylcholine. J. Biol. Chem. 1996 Jul 7/26/1996; 271(30): 18114-21. PMID: 8663471, ISSN: 0021-9258.

Malcolm KC, Elliott CM, Exton JH. Evidence for Rho-mediated agonist stimulation of phospholipase D in rat1 fibroblasts. Effects of Clostridium botulinum C3 exoenzyme. J. Biol. Chem. 1996 May 5/31/1996; 271(22): 13135-9. PMID: 8662844, ISSN: 0021-9258.

Venkatakrishnan G, Exton JH. Identification of determinants in the alpha-subunit of Gq required for phospholipase C activation. J. Biol. Chem. 1996 Mar 3/1/1996; 271(9): 5066-72. PMID: 8617784, ISSN: 0021-9258.

Pete MJ, Wu DW, Exton JH. Subcellular fractions of bovine brain degrade phosphatidylcholine by sequential deacylation of the sn-1 and sn-2 positions. Biochim. Biophys. Acta. 1996 Feb 2/16/1996; 1299(3): 325-32. PMID: 8597587, ISSN: 0006-3002.

Venkatakrishnan, G. and Exton, J.H. Identification of determinants in the alpha subunit of G(q) required for phospholipase C activation. J. Biol. Chem. 1996; 271: 5066-72.

Fleming, I.N. and Exton, J.H. Differential translocation of Rho-family GTPases by lysophosphatidic acid, endothelin-1 and platelet-derived growth factor. J. Biol. Chem. 1996; 271: 33067-73.

Malcolm, K.C., Elliott, C.M. and Exton, J.H. Evidence for Rho-mediated agonist stimulation of phospholipase D in Rat1 fibroblasts. Effects of Clostridium botulinum C3 exoenzyme. J. Biol. Chem. 1996; 271: 13135-9.

Malcolm KC, Trammell SE, Exton JH. Purinergic agonist and G protein stimulation of phospholipase D in rat liver plasma membranes. Independence from phospholipase C activation. Biochim. Biophys. Acta. 1995 Aug 8/31/1995; 1268(2): 152-8. PMID: 7662702, ISSN: 0006-3002.

Pete MJ, Exton JH. Phospholipid interactions affect substrate hydrolysis by bovine brain phospholipase A1. Biochim. Biophys. Acta. 1995 Jun 6/6/1995; 1256(3): 367-73. PMID: 7786901, PII: 0005-2760(95)00047-G, ISSN: 0006-3002.

Siddiqi AR, Smith JL, Ross AH, Qiu RG, Symons M, Exton JH. Regulation of phospholipase D in HL60 cells. Evidence for a cytosolic phospholipase D. J. Biol. Chem. 1995 Apr 4/14/1995; 270(15): 8466-73. PMID: 7721742, ISSN: 0021-9258.

Siddiqi, A.R., Smith, J.L., Ross, A.H., Qiu, R.-G., Symons, M. and Exton, J.H. Regulation of phospholipase D in HL60 cells. Evidence for a cytosolic phospholipase D. J. Biol. Chem. 1995; 270: 8466-73.

Yeo EJ, Kazlauskas A, Exton JH. Activation of phospholipase C-gamma is necessary for stimulation of phospholipase D by platelet-derived growth factor. J. Biol. Chem. 1994 Nov 11/11/1994; 269(45): 27823-6. PMID: 7961710, ISSN: 0021-9258.

Pete MJ, Ross AH, Exton JH. Purification and properties of phospholipase A1 from bovine brain. J. Biol. Chem. 1994 Jul 7/29/1994; 269(30): 19494-500. PMID: 8034719, ISSN: 0021-9258.

Conricode KM, Smith JL, Burns DJ, Exton JH. Phospholipase D activation in fibroblast membranes by the alpha and beta isoforms of protein kinase C. FEBS Lett. 1994 Apr 4/4/1994; 342(2): 149-53. PMID: 8143868, PII: 0014-5793(94)80490-7, ISSN: 0014-5793.

Exton JH. Messenger molecules derived from membrane lipids. Curr. Opin. Cell Biol. 1994 Apr; 6(2): 226-9. PMID: 8024814, ISSN: 0955-0674.

Exton JH. Phosphoinositide phospholipases and G proteins in hormone action. Annu. Rev. Physiol. 1994; 56: 349-69. PMID: 8010744, DOI: 10.1146/annurev.ph.56.030194.002025, ISSN: 0066-4278.

Malcolm, K.C., Ross, A.H., Qiu, R.-G., Symons, M. and Exton, J.H. Activation of rat liver phospholipase D by the small GTP- binding protein rhoA. J. Biol. Chem. 1994; 269: 25951-4.

Yeo, E.-J., Kazlauskas, A. and Exton, J.H. Activation of phospholipase C-gamma is necessary for stimulation of phospholipase D by platelet-derived growth factor. 27823-27826. 1994; 269: J. Biol. Chem.

Pete, M.J., Ross, A.H. and Exton, J.H. Purification and properties of phospholipase A1 from bovine brain. J. Biol. Chem. 1994; 269: 19494-500.

Ha KS, Exton JH. Activation of actin polymerization by phosphatidic acid derived from phosphatidylcholine in IIC9 fibroblasts. J. Cell Biol. 1993 Dec; 123(6 Pt 2): 1789-96. PMID: 8276897, PMCID: PMC2290890, ISSN: 0021-9525.

Blank JL, Shaw K, Ross AH, Exton JH. Purification of a 110-kDa phosphoinositide phospholipase C that is activated by G-protein beta gamma-subunits. J. Biol. Chem. 1993 Nov 11/25/1993; 268(33): 25184-91. PMID: 8227082, ISSN: 0021-9258.

Allan CJ, Exton JH. Quantification of inositol phospholipid breakdown in isolated rat hepatocytes. Biochem. J. 1993 Mar 3/15/1993; 290 ( Pt 3): 865-72. PMID: 8384449, PMCID: PMC1132361, ISSN: 0264-6021.

Nakanishi H, Brewer KA, Exton JH. Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 1993 Jan 1/5/1993; 268(1): 13-6. PMID: 8380153, ISSN: 0021-9258.

Exton JH. Role of G proteins in activation of phosphoinositide phospholipase C. Adv. Second Messenger Phosphoprotein Res. 1993; 28: 65-72. PMID: 8398419, ISSN: 1040-7952.

Ha, K.-S. and Exton, J.H. Differential translocation of protein kinase C isozymes by thrombin and platelet-derived growth factor. J. Biol. Chem. 1993; 268: 10534-9.

Siddiqui RA, Exton JH. Oleate stimulation of diacylglycerol formation from phosphatidylcholine through effects on phospholipase D and phosphatidate phosphohydrolase. Eur. J. Biochem. 1992 Dec 12/1/1992; 210(2): 601-7. PMID: 1459142, ISSN: 0014-2956.

Blank JL, Brattain KA, Exton JH. Activation of cytosolic phosphoinositide phospholipase C by G-protein beta gamma subunits. J. Biol. Chem. 1992 Nov 11/15/1992; 267(32): 23069-75. PMID: 1331076, ISSN: 0021-9258.

Shaw K, Exton JH. Identification in bovine liver plasma membranes of a Gq-activatable phosphoinositide phospholipase C. Biochemistry. 1992 Jul 7/14/1992; 31(27): 6347-54. PMID: 1320935, ISSN: 0006-2960.

Siddiqui RA, Exton JH. Phospholipid base exchange activity in rat liver plasma membranes. Evidence for regulation by G-protein and P2y-purinergic receptor. J. Biol. Chem. 1992 Mar 3/25/1992; 267(9): 5755-61. PMID: 1313419, ISSN: 0021-9258.

Blank, J.L., Brattain, K.A. and Exton, J.H. Activation of cytosolic phosphoinositide phospholipase C by G-protein beta gamma subunits. J. Biol. Chem. 1992; 267: 23069-75.

Berstein, G., Blank, J.L., Exton, J.H. and Ross, E.M. Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified m1 muscarinic receptor, Gq/11 and phospholipase C-beta 1. J. Biol. Chem. 1992; 267: 8081-8.

Conricode, K.M. and Exton, J.H. Activation of phospholipase D by protein kinase C. Evidence for a phosphorylation independent mechanism. J. Biol. Chem. 1992; 267: 7199-202.

Nakanishi, H. and Exton, J.H. Purification and characterization of the zeta isoform of protein kinase C from bovine kidney. J. Biol. Chem. 1992; 267: 16347-54.

Berstein, G., Blank, J.L., Jhon, D.-Y., Exton, J.H., Rhee, S.G. and Ross, E.M. Phospholipase C-1 is a GTPase activating protein (GAP) for Gq/11, its physiologic regulator. Cell. 1992; 70: 411-8.

Stewart SJ, Cunningham GR, Strupp JA, House FS, Kelley LL, Henderson GS, Exton JH, Bocckino SB. Activation of phospholipase D: a signaling system set in motion by perturbation of the T lymphocyte antigen receptor/CD3 complex. Cell Regul. 1991 Oct; 2(10): 841-50. PMID: 1839358, PMCID: PMC361879, ISSN: 1044-2030.

Blank JL, Ross AH, Exton JH. Purification and characterization of two G-proteins that activate the beta 1 isozyme of phosphoinositide-specific phospholipase C. Identification as members of the Gq class. J. Biol. Chem. 1991 Sep 9/25/1991; 266(27): 18206-16. PMID: 1655741, ISSN: 0021-9258.

Bocckino SB, Wilson PB, Exton JH. Phosphatidate-dependent protein phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 1991 Jul 7/15/1991; 88(14): 6210-3. PMID: 2068102, PMCID: PMC52052, ISSN: 0027-8424.

Wange RL, Smrcka AV, Sternweis PC, Exton JH. Photoaffinity labeling of two rat liver plasma membrane proteins with [32P]gamma-azidoanilido GTP in response to vasopressin. Immunologic identification as alpha subunits of the Gq class of G proteins. J. Biol. Chem. 1991 Jun 6/25/1991; 266(18): 11409-12. PMID: 1646803, ISSN: 0021-9258.

Exton JH, Taylor SJ, Augert G, Bocckino SB. Cell signalling through phospholipid breakdown. Mol. Cell. Biochem. 1991 May 5/29/1991; 104(1-2): 81-6. PMID: 1656198, ISSN: 0300-8177.

Exton JH. Some thoughts on the mechanism of action of insulin. Diabetes. 1991 May; 40(5): 521-6. PMID: 1902425, ISSN: 0012-1797.

Taylor SJ, Chae HZ, Rhee SG, Exton JH. Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins. Nature. 1991 Apr 4/11/1991; 350(6318): 516-8. PMID: 1707501, DOI: 10.1038/350516a0, ISSN: 0028-0836.

Taylor, S.J., Chae, H.Z., Rhee, S.G. and Exton, J.H. Activation of the Beta 1 isozyme of phospholipase C by purified a subunits of the G(q) class of G proteins. Nature. 1991; 350: 516-8.

Blank, J.L., Ross, A.H. and Exton, J.H. Purification and characterization of two G-proteins which activate the beta 1 isozyme of phosphoinositide-specific phospholipase C. Identification as members of the G(q) class. J. Biol. Chem. 1991; 266: 17206-8216.

Bouscarel B, Augert G, Taylor SJ, Exton JH. Alterations in vasopressin and angiotensin II receptors and responses during culture of rat liver cells. Biochim. Biophys. Acta. 1990 Dec 12/10/1990; 1055(3): 265-72. PMID: 2265214, ISSN: 0006-3002.

Georgoussi Z, Taylor SJ, Bocckino SB, Exton JH. Purification of the hepatic vasopressin receptor using a novel affinity column. Biochim. Biophys. Acta. 1990 Oct 10/15/1990; 1055(1): 69-74. PMID: 2171678, PII: 0167-4889(90)90092-R, ISSN: 0006-3002.

Taylor SJ, Smith JA, Exton JH. Purification from bovine liver membranes of a guanine nucleotide-dependent activator of phosphoinositide-specific phospholipase C. Immunologic identification as a novel G-protein alpha subunit. J. Biol. Chem. 1990 Oct 10/5/1990; 265(28): 17150-6. PMID: 2120213, ISSN: 0021-9258.

Exton JH. Signaling through phosphatidylcholine breakdown. J. Biol. Chem. 1990 Jan 1/5/1990; 265(1): 1-4. PMID: 2104616, ISSN: 0021-9258.

Exton JH. Hormonal regulation of phosphatidylcholine breakdown. Adv. Second Messenger Phosphoprotein Res. 1990; 24: 152-7. PMID: 1976328, ISSN: 1040-7952.

Augert G, Bocckino SB, Blackmore PF, Exton JH. Hormonal stimulation of diacylglycerol formation in hepatocytes. Evidence for phosphatidylcholine breakdown. J. Biol. Chem. 1989 Dec 12/25/1989; 264(36): 21689-98. PMID: 2513325, ISSN: 0021-9258.

Bocckino SB, Wilson PB, Exton JH. An early elevation of diacylglycerol and phosphatidate in regenerating liver. Biochem. Biophys. Res. Commun. 1989 Oct 10/16/1989; 164(1): 290-4. PMID: 2803302, PII: 0006-291X(89)91716-6, ISSN: 0006-291X.

Lynch CJ, Blackmore PF, Johnson EH, Wange RL, Krone PK, Exton JH. Guanine nucleotide binding regulatory proteins and adenylate cyclase in livers of streptozotocin- and BB/Wor-diabetic rats. Immunodetection of Gs and Gi with antisera prepared against synthetic peptides. J. Clin. Invest. 1989 Jun; 83(6): 2050-62. PMID: 2498395, PMCID: PMC303930, DOI: 10.1172/JCI114116, ISSN: 0021-9738.

Augert G, Blackmore PF, Exton JH. Changes in the concentration and fatty acid composition of phosphoinositides induced by hormones in hepatocytes. J. Biol. Chem. 1989 Feb 2/15/1989; 264(5): 2574-80. PMID: 2536716, ISSN: 0021-9258.

Stewart SJ, Prpic V, Johns JA, Powers FS, Graber SE, Forbes JT, Exton JH. Bacterial toxins affect early events of T lymphocyte activation. J. Clin. Invest. 1989 Jan; 83(1): 234-42. PMID: 2536043, PMCID: PMC303667, DOI: 10.1172/JCI113865, ISSN: 0021-9738.

Augert, G., Blackmore, P.F. and Exton, J.H. Changes in the concentration and fatty acid composition of phosphoinositides induced by hormones in hepatocytes. J. Biol. Chem. 1989; 264: 2574-80.

Augert, G., Bocckino, S.B., Blackmore, P.F.and Exton, J.H. Hormonal stimulation of diacylglycerol formation in hepatocytes. Evidence for phosphatidylcholine breakdown. J. Biol. Chem. 1989; 264: 21689-98.

Bouscarel B, Wilson PB, Blackmore PF, Lynch CJ, Exton JH. Agonist-induced down-regulation of the angiotensin II receptor in primary cultures of rat hepatocytes. J. Biol. Chem. 1988 Oct 10/15/1988; 263(29): 14920-4. PMID: 3139662, ISSN: 0021-9258.

Bouscarel B, Blackmore PF, Exton JH. Characterization of the angiotensin II receptor in primary cultures of rat hepatocytes. Evidence that a single population is coupled to two different responses. J. Biol. Chem. 1988 Oct 10/15/1988; 263(29): 14913-9. PMID: 2844791, ISSN: 0021-9258.

Exton JH. Mechanisms of action of calcium-mobilizing agonists: some variations on a young theme. FASEB J. 1988 Aug; 2(11): 2670-6. PMID: 2456243, ISSN: 0892-6638.

Bouscarel B, Meurer K, Decker C, Exton JH. The role of protein kinase C in the inactivation of hepatic glycogen synthase by calcium-mobilizing agonists. Biochem. J. 1988 Apr 4/1/1988; 251(1): 47-53. PMID: 3134012, PMCID: PMC1148962, ISSN: 0264-6021.

Augert G, Exton JH. Insulin and oxytocin effects on phosphoinositide metabolism in adipocytes. J. Biol. Chem. 1988 Mar 3/15/1988; 263(8): 3600-9. PMID: 2831195, ISSN: 0021-9258.

Lynch CJ, Taylor SJ, Smith JA, Exton JH. Formation of the high-affinity agonist state of the alpha 1-adrenergic receptor at cold temperatures does not require a G-protein. FEBS Lett. 1988 Feb 2/29/1988; 229(1): 54-8. PMID: 2831091, PII: 0014-5793(88)80796-8, ISSN: 0014-5793.

Blackmore PF, Lynch CJ, Uhing RJ, Fitzgerald T, Bocckino SB, Exton JH. Role of guanine nucleotide regulatory proteins and inositol phosphates in the hormone induced mobilization of hepatocyte calcium. Adv. Exp. Med. Biol. 1988; 232: 169-82. PMID: 3145679, ISSN: 0065-2598.

Exton JH. Role of phosphoinositides in the regulation of liver function. Hepatology. 1988 Jan; 8(1): 152-66. PMID: 2448216, ISSN: 0270-9139.

Lynch CJ, Bocckino SB, Blackmore PF, Exton JH. Calcium-mobilizing hormones and phorbol myristate acetate mediate heterologous desensitization of the hormone-sensitive hepatic Na+/K+ pump. Biochem. J. 1987 Dec 12/15/1987; 248(3): 807-13. PMID: 3435486, PMCID: PMC1148621, ISSN: 0264-6021.

Taylor SJ, Exton JH. Guanine-nucleotide and hormone regulation of polyphosphoinositide phospholipase C activity of rat liver plasma membranes. Bivalent-cation and phospholipid requirements. Biochem. J. 1987 Dec 12/15/1987; 248(3): 791-9. PMID: 2829842, PMCID: PMC1148619, ISSN: 0264-6021.

Bocckino SB, Wilson PB, Exton JH. Ca2+-mobilizing hormones elicit phosphatidylethanol accumulation via phospholipase D activation. FEBS Lett. 1987 Dec 12/10/1987; 225(1-2): 201-4. PMID: 3319693, PII: 0014-5793(87)81157-2, ISSN: 0014-5793.

Exton JH. Calcium signalling in cells--molecular mechanisms. Kidney Int. Suppl. 1987 Dec; 23: S68-81. PMID: 2831426, ISSN: 0098-6577.

Irving, H. and Exton, J.H. Phosphatidylcholine breakdown in rat liver plasma membranes. J.Biol.Chem. 1987; 262: 3440-3.

Bocckino, S.B., Blackmore, P.F., Wilson, P.B., and Exton, J.H. Phosphatidate accumulation in hormone-treated hepatocytes via a phospholipase D mechanism. J. Biol. Chem. 1987; 262: 15309-15.