Research Topics
Genomes and Genes
| J A WilliamsSummaryAffiliation: University of Michigan Country: USA Publications
Research Grants
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Detail Information
Publications
Regulation of pancreatic acinar cell functionJohn A Williams
Departments of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
Curr Opin Gastroenterol 22:498-504. 2006..This review identifies and puts into context those articles which further our understanding in this area...- Receptor-mediated signal transduction pathways and the regulation of pancreatic acinar cell functionJohn A Williams
Department of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, MI 48109 5622, USA
Curr Opin Gastroenterol 24:573-9. 2008..This review identifies and puts into context these recent studies, which further understanding in these areas... - Cholecystokinin activates a variety of intracellular signal transduction mechanisms in rodent pancreatic acinar cellsJohn A Williams
Department of Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Pharmacol Toxicol 91:297-303. 2002..Further work is needed to understand how CCK receptors activate most of the above pathways and to better understand the biological events regulated by these diverse signaling pathways... - Small G proteins as key regulators of pancreatic digestive enzyme secretionJohn A Williams
Dept of Molecular and Integrative Physiology, Univ of Michigan, Ann Arbor, MI 48109, USA
Am J Physiol Endocrinol Metab 296:E405-14. 2009..The Rho family small G proteins RhoA and Rac1 also regulate secretion through remodeling of the actin cytoskeleton. Possible mechanisms for regulation of these G proteins and their effector molecules are considered... - Intracellular signaling mechanisms activated by cholecystokinin-regulating synthesis and secretion of digestive enzymes in pancreatic acinar cellsJ A Williams
Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109 0622, USA
Annu Rev Physiol 63:77-97. 2001..CCK also activates a number of tyrosyl phosphorylation events including that of p125FAK and other proteins associated with focal adhesions... - A role for the p38 mitogen-activated protein kinase/Hsp 27 pathway in cholecystokinin-induced changes in the actin cytoskeleton in rat pancreatic aciniC Schafer
Department of Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109 0622, USA
J Biol Chem 273:24173-80. 1998..Activation of p38 MAP kinase, most likely through phosphorylation of Hsp 27, plays a role in the organization of the actin cytoskeleton in pancreatic acini... - A role for Rho and Rac in secretagogue-induced amylase release by pancreatic aciniYan Bi
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, USA
Am J Physiol Cell Physiol 289:C22-32. 2005..These data suggest that Rho and Rac are both involved in CCK-induced amylase release in pancreatic acinar cell possibly through an effect on the actin cytoskeleton... - Regulator of calcineurin 1 controls growth plasticity of adult pancreasGrzegorz T Gurda
Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, Michigan, USA
Gastroenterology 139:609-19, 619.e1-6. 2010..CCK-driven pancreatic growth requires calcineurin (CN), which activates Nuclear Factor of Activated T cells (NFATs), but the genetic underpinnings and feedback mechanisms that regulate this response are not known... - Rho and Rac promote acinar morphological changes, actin reorganization, and amylase secretionYan Bi
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
Am J Physiol Gastrointest Liver Physiol 289:G561-70. 2005.... - Calcineurin mediates pancreatic growth in protease inhibitor-treated miceMitsuo Tashiro
Molecular and Integrative Physiology, Univ. of Michigan Medical School, 7744 Medical Science II, Ann Arbor, MI 48109-0622, USA
Am J Physiol Gastrointest Liver Physiol 286:G784-90. 2004..In conclusion, activation and possibly upregulation of CN may participate in regulation of pancreatic growth by CCK in mice... - Induction of early response genes in trypsin inhibitor-induced pancreatic growthLili Guo
Dept of Molecular and Integrative Physiology, Univ of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
Am J Physiol Gastrointest Liver Physiol 292:G667-77. 2007..These results indicate that camostat feeding induces a spectrum of early response gene expression and AP-1 DNA binding and that these effects are mainly CCK dependent... - Calcineurin-dependent and calcineurin-independent signal transduction pathways activated as part of pancreatic growthMitsuo Tashiro
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109-0622, USA
Pancreas 32:314-20. 2006..CONCLUSIONS: The pancreatic growth response is accompanied by activation of a number of signaling pathways regulating transcription and translation, some of which are dependent on and some independent of calcineurin... - CCK-independent mTORC1 activation during dietary protein-induced exocrine pancreas growthStephen J Crozier
Department of 1Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
Am J Physiol Gastrointest Liver Physiol 299:G1154-63. 2010..Prolonged mTORC1 activation is thus required for dietary protein-induced pancreatic growth in the absence of CCK... - Purification and characterization of a novel physiological substrate for calcineurin in mammalian cellsG E Groblewski
Department of Physiology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109 0622, USA
J Biol Chem 273:22738-44. 1998..The ubiquitous expression of CRHSP-24 in rat tissues suggests that this novel calcineurin substrate plays a common role in calcium-mediated signal transduction... - Arginine induced acute pancreatitis alters the actin cytoskeleton and increases heat shock protein expression in rat pancreatic acinar cellsM Tashiro
Department of Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0622, USA
Gut 49:241-50. 2001..The present work in conjunction with earlier work on caerulein induced pancreatitis indicates that changes in the actin cytoskeleton are an early component in experimental pancreatitis... - Identification of Rab 5 but not Rab 3A in rat pancreatic zymogen granule membranesA C Wagner
Department of Physiology, University of Michigan, Ann Arbor 48109
Biochem Biophys Res Commun 200:542-8. 1994..Of these, Rab 5 was identified in purified zymogen granule membranes where it may be involved in the endocytotic retrieval of granule membrane following exocytosis... - Global topology analysis of pancreatic zymogen granule membrane proteinsXuequn Chen
Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
Mol Cell Proteomics 7:2323-36. 2008..This model contributes to a firm foundation for developing a higher order architecture model of the ZGM and for future functional studies of individual ZGM proteins... - Rab27b localizes to zymogen granules and regulates pancreatic acinar exocytosisXuequn Chen
Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, MI, USA
Biochem Biophys Res Commun 323:1157-62. 2004..This enhancement and inhibition occurred at all points on the CCK dose-response curve and over a 30min time course. These results demonstrate that Rab27b is present on ZGs and plays an important role in regulating acinar exocytosis... - Rap1 activation plays a regulatory role in pancreatic amylase secretionMaria E Sabbatini
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109 0622, USA
J Biol Chem 283:23884-94. 2008..Rap1 activation not only mediates the cAMP-evoked response via Epac1 but is also involved in CCK- and carbachol-induced amylase release, with their action most likely mediated by CalDAG-GEF III... - Activation of the mTOR signalling pathway is required for pancreatic growth in protease-inhibitor-fed miceStephen J Crozier
Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
J Physiol 573:775-86. 2006..We conclude that the mTOR signalling pathway is required for CCK-induced cell division and pancreatic growth... - CCK-induced pancreatic growth is not limited by mitogenic capacity in miceStephen J Crozier
Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
Am J Physiol Gastrointest Liver Physiol 294:G1148-57. 2008..These results indicate that CCK-stimulated growth of the pancreas is not limited by acinar cell mitogenic capacity but is due, at least in part, to inhibition of promitogenic Akt signaling... - Cholecystokinin activates pancreatic calcineurin-NFAT signaling in vitro and in vivoGrzegorz T Gurda
Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
Mol Biol Cell 19:198-206. 2008..The changes also required calcineurin, as they were blocked by FK506. We conclude that CCK activates NFATs in a calcineurin-dependent manner, both in vitro and in vivo... - Organellar proteomics: analysis of pancreatic zymogen granule membranesXuequn Chen
Department of Biological Chemistry, The University of Michigan, Ann Arbor, Michigan 48109, USA
Mol Cell Proteomics 5:306-12. 2006.... - Molecular mechanisms of pancreatic dysfunction induced by protein malnutritionStephen J Crozier
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109 5622, USA
Gastroenterology 137:1093-101, 1101.e1-3. 2009..The purpose of this study was to elucidate the role of mTOR in protein deficiency-induced pancreatic dysfunction... - Regulation of translation elongation and phosphorylation of eEF2 in rat pancreatic aciniMaria Dolors Sans
Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
Biochem Biophys Res Commun 319:144-51. 2004..Translation elongation in pancreatic acinar cells is likely regulated by eEF2 through the mTOR, p38, and MEK pathways, and modulated through PP2A... - Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4FMaria Dolors Sans
Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, MI 48109 0622, USA
Am J Physiol Gastrointest Liver Physiol 285:G517-28. 2003.... - Regulation of CCK-induced amylase release by PKC-delta in rat pancreatic acinar cellsChenwei Li
Dept of Molecular and Integrative Physiology, Univ of Michigan, 7744 Medical Science II, Ann Arbor, MI 48109 0622, USA
Am J Physiol Gastrointest Liver Physiol 287:G764-71. 2004..GF109203X totally blocked the enhancement of amylase release by PKC-delta but had no further effect in the presence of dominant-negative PKC-delta. These results indicate that PKC-delta is the PKC isoform involved with amylase secretion... - Effect of CCK and intracellular calcium to regulate eIF2B and protein synthesis in rat pancreatic acinar cellsMaria Dolors Sans
Department of Physiology, University of Michigan, 1301 St Catherine St, 7737 Med Sci II, Ann Arbor, MI 48109, USA
Am J Physiol Gastrointest Liver Physiol 282:G267-76. 2002.... - Translational control of protein synthesis in pancreatic acinar cellsMaria Dolors Sans
Department of Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Int J Gastrointest Cancer 31:107-15. 2002..eIF4E is itself phosphorylated by a distinct pathway. Inhibition of acinar protein synthesis can be mediated by inhibition of eIF2B following phosphorylation of eIF2alpha... - Quantitative organellar proteomics analysis of rough endoplasmic reticulum from normal and acute pancreatitis rat pancreasXuequn Chen
Departments of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, Michigan 48109, USA
J Proteome Res 9:885-96. 2010..These results suggest that the early stages of AP involve changes of multiple RER proteins that may affect the synthesis and processing of digestive enzymes... - Dominant negative Rab3D mutants reduce GTP-bound endogenous Rab3D in pancreatic aciniXuequn Chen
Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, Michigan 48109, USA
J Biol Chem 278:50053-60. 2003..6 +/- 3.3%. The two dominant negative Rab3D mutants, therefore, interfere with endogenous Rab3D function by blocking the GDP/GTP exchange but not zymogen granule targeting of endogenous Rab3D... - Secretagogue-stimulated pancreatic secretion is differentially regulated by constitutive NOS isoforms in miceMatthew J DiMagno
Department of Internal Medicine, The University of Michigan Medical School, 1500 E Medical Center Dr, 3912 Taubman Center, Ann Arbor, MI 48109 0362, USA
Am J Physiol Gastrointest Liver Physiol 286:G428-36. 2004..eNOS likely plays a dominant role, because eNOS deletion mimics NOS blockade by inhibiting CCK-8 and carbachol-stimulated secretion, whereas nNOS deletion augments CCK-8 but not carbachol-stimulated secretion... - CCK activates RhoA and Rac1 differentially through Galpha13 and Galphaq in mouse pancreatic aciniMaria E Sabbatini
Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, Michigan, USA
Am J Physiol Cell Physiol 298:C592-601. 2010..CCK-induced actin cytoskeletal reorganization is mainly mediated by Galpha(q). By contrast, Galpha(13) and Galpha(q) signaling are required for CCK-induced amylase secretion... - Endothelial nitric oxide synthase is protective in the initiation of caerulein-induced acute pancreatitis in miceMatthew J DiMagno
Department of Internal Medicine, Division of Gastroenterology, The University of Michigan Medical School, 1500 E Medical Center Drive, 3912 Taubman Center, Ann Arbor, MI 48109 0362, USA
Am J Physiol Gastrointest Liver Physiol 287:G80-7. 2004..Thus eNOS is the main isoform influencing the initiation of caerulein-induced AP. eNOS-derived NO exerts a protective effect through actions on nonacinar cell types, most likely endothelial cells, to produce greater PMBF... - Calcineurin is required for translational control of protein synthesis in rat pancreatic aciniMaria Dolors Sans
Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1301 E Catherine St, 7737 Med Sci II, Ann Arbor, MI 48109 0622, USA
Am J Physiol Cell Physiol 287:C310-9. 2004..From these results, we conclude that calcineurin activity is required for protein synthesis, and this action may be related to an effect on the formation of the mRNA cap binding complex and the elongation processes... - Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNAMaria Dolors Sans
Department of Molecular and Integrative Physiology, The University of Michigan Medical School, Ann Arbor, Michigan 48109 0622, USA
Am J Physiol Gastrointest Liver Physiol 287:G667-75. 2004..By contrast, feeding did not affect eIF2B activity. Thus food intake stimulates pancreatic protein synthesis and translational effectors without increasing digestive enzyme mRNA levels... - Dominant negative Rab3D inhibits amylase release from mouse pancreatic aciniXuequn Chen
Department of Physiology, The University of Michigan, Ann Arbor, Michigan 48109 0622, USA
J Biol Chem 277:18002-9. 2002..These results suggest that Rab3D plays an important role in regulating the terminal steps of acinar exocytosis and that this effect is greatest on the early phase of amylase release... - Activation of MAP kinase kinase (MEK) and Ras by cholecystokinin in rat pancreatic aciniR D Duan
Department of Physiology, University of Michigan, Ann Arbor 48109, USA
Am J Physiol 268:G1060-5. 1995..In conclusion, the activation of MAP kinase by CCK can be explained by activation of MEK and may involve the activation of Ras by a protein kinase C-dependent mechanism... - Stress kinases and heat shock proteins in the pancreas: possible roles in normal function and diseaseC Schafer
Department of Physiology 7737 Medical Science II, University of Michigan, Ann Arbor, 48109 0622, USA
J Gastroenterol 35:1-9. 2000..This review will summarize current knowledge of the regulation and function of stress-activated kinases and stress proteins in the pancreas... - A single mutation converts a novel phosphotyrosine binding domain into a dual-specificity phosphataseM J Wishart
Department of Physiology, University of Michigan, Ann Arbor 48109 0606, USA
J Biol Chem 270:26782-5. 1995..We believe this is the first example of a naturally occurring "dominant negative" phosphotyrosine/serine/threonine-binding protein which is structurally related to dsPTPases... - Identification of calcineurin regulated phosphorylation sites on CRHSP-24SaeHong Lee
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Biochem Biophys Res Commun 385:413-7. 2009.... - Hyperthermia induces multiple pancreatic heat shock proteins and protects against subsequent arginine-induced acute pancreatitis in ratsMitsuo Tashiro
Department of Physiology, University of Michigan Medical School, Ann Arbor, 48109-0622, USA
Digestion 65:118-26. 2002.... - Regulation of acinar cell function in the pancreasJohn A Williams
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109 5622, USA
Curr Opin Gastroenterol 26:478-83. 2010..This review identifies and puts into context the recent articles which have advanced understanding of the functions of pancreatic acinar cells and the mechanisms by which these functions are regulated... - Cyclosporin A inhibits Ca2+/calmodulin-dependent protein phosphatase and secretion in pancreatic acinar cellsG E Groblewski
Department of Physiology, University of Michigan, Ann Arbor 48109
J Biol Chem 269:15111-7. 1994..Collectively, these data indicate that the Ca2+/calmodulin-dependent protein phosphatase, PP2B, plays a significant role in stimulus-secretion coupling in pancreatic acinar cells... - Secretin is not necessary for exocrine pancreatic development and growth in miceMaria Dolors Sans
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, 48109 5622, USA
Am J Physiol Gastrointest Liver Physiol 301:G791-8. 2011..Camostat-fed littermate secretin and secretin receptor-deficient mice had similar pancreatic mass to WT mice. These results indicate that secretin is not required for normal pancreatic development or adaptive growth mediated by CCK... - CCK-A receptor activates RhoA through G alpha 12/13 in NIH3T3 cellsSophie L Le Page
Department. of Molecular and Integrative Physiology, University of Michigan, 7744 Medical Science II, Ann Arbor, MI 48109-0622, USA
Am J Physiol Cell Physiol 285:C1197-206. 2003..These results show that in NIH3T3 cells bearing CCK-A receptors, CCK activates Rho primarily through G13, leading to rearrangement of the actin cytoskeleton... - Overexpression of heat shock protein Hsp27 protects against cerulein-induced pancreatitisConstanze Kubisch
Department of Internal Medicine II, Klinikum Grosshadern, Ludwig Maximilians University Munich, Germany
Gastroenterology 127:275-86. 2004.... - Leucine activates pancreatic translational machinery in rats and mice through mTOR independently of CCK and insulinMaria Dolors Sans
Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA 17033, USA
J Nutr 136:1792-9. 2006..We conclude that leucine may participate, as a signal as well as a substrate, in activating the translational machinery in pancreatic acinar cells independently of hormonal effects and that this action is through the mTOR pathway... - Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapibRonald W Clark
Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton, Conn 06340, USA
Arterioscler Thromb Vasc Biol 24:490-7. 2004.... - Early activation of endoplasmic reticulum stress is associated with arginine-induced acute pancreatitisConstanze H Kubisch
Department of Cancer Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77230-1429, USA
Am J Physiol Gastrointest Liver Physiol 291:G238-45. 2006..These results indicate that ER stress is an important early acinar cell event that likely contributes to the development of acute pancreatitis in the arginine model... - International symposium: mechanism of pancreatitis--between bedside and laboratoryMakoto Otsuki
University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan
Pancreas 24:391-407. 2002
Research Grants
- Dietary Regulation of Pancreatic Digestive EnzymesJohn Williams; Fiscal Year: 2006..This work, in addition to understanding normal function may assist in designing diets to maximally stimulate pancreatic growth to counteract pancreatic insufficiency. ..
- Systems and Integrative Biology Training GrantJohn Williams; Fiscal Year: 2007....
- Dietary Regulation of Pancreatic Digestive EnzymesJohn A Williams; Fiscal Year: 2010..Knowledge from this project should allow designing approaches to assist the human pancreas to regenerate and ensure an adequate supply of pancreatic digestive enzymes. ..
- NOVEL KINASE SIGNALING CASCADES IN PANCREATIC ACINIJohn Williams; Fiscal Year: 2002..While the work is aimed at understanding the pancreatic acinar cell, it will also have implications for the regulation of other gastrointestinal cell types. ..
- CALCIUM AND PANCREATIC STIMULUS-SECRETION COUPLINGJohn Williams; Fiscal Year: 1993..These studies are also relevant to understanding of the abnormal secretion seen in pancreatic diseases such as pancreatitis and cancer...
- Dietary Regulation of Pancreatic Digestive EnzymesJohn Williams; Fiscal Year: 2009..Knowledge from this project should allow designing approaches to assist the human pancreas to regenerate and ensure an adequate supply of pancreatic digestive enzymes. ..