Growth Suppression Mechanism of Connexin 37 in Response to Phosphorylation State of the Carboxy Terminus

Persistent Link:
http://hdl.handle.net/10150/243974
Title:
Growth Suppression Mechanism of Connexin 37 in Response to Phosphorylation State of the Carboxy Terminus
Author:
Jacobsen, Nicole Lynne; Nelson, Tasha K.; Burt, Janis M.
Issue Date:
May-2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Connexin 37 (Cx37), profoundly suppresses the growth of rat insulinoma (Rin) cells and requires a functional channel. To determine if the CT is necessary for Cx37-mediated growth suppression, a series of deletions and mutations affecting the availability of putative phosphorylation sites in the region of 273-333 of Cx37 were generated. Truncation at P273 alleviated the growth suppressive effect of Cx37 while retaining channel functionality. Interestingly, substate behavior is lost in iRin37-273tr. Based on the observation of run-down behavior in Cx37-wt channels consistent with dialysis of PKC, TPA and BIM treatment of Cx37- wt channels revealed that PKC activation generates a higher incidence of high conductance channels whereas BIM treatment results in the converse. Exploiting this observation, a S-Ax3 mutation targeting known MAPK and PKC sites aligned from Cx43, was generated. However, channels are able to reside in the sub-conductance state and cells are anti-proliferative. Four additional serine to alanine mutations at putative phosphorylation sites (>90%) were made to generate an S7A mutation and did not dispel the growth suppressive effect of Cx37. A phosphomimetic S7D mutation appears to induce cell death. Based on these data, it appears that substate behavior regulated by the CT is indicative growth suppression by Cx37.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Nutritional Sciences
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleGrowth Suppression Mechanism of Connexin 37 in Response to Phosphorylation State of the Carboxy Terminusen_US
dc.creatorJacobsen, Nicole Lynneen_US
dc.contributor.authorJacobsen, Nicole Lynneen_US
dc.contributor.authorNelson, Tasha K.en_US
dc.contributor.authorBurt, Janis M.en_US
dc.date.issued2012-05-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractConnexin 37 (Cx37), profoundly suppresses the growth of rat insulinoma (Rin) cells and requires a functional channel. To determine if the CT is necessary for Cx37-mediated growth suppression, a series of deletions and mutations affecting the availability of putative phosphorylation sites in the region of 273-333 of Cx37 were generated. Truncation at P273 alleviated the growth suppressive effect of Cx37 while retaining channel functionality. Interestingly, substate behavior is lost in iRin37-273tr. Based on the observation of run-down behavior in Cx37-wt channels consistent with dialysis of PKC, TPA and BIM treatment of Cx37- wt channels revealed that PKC activation generates a higher incidence of high conductance channels whereas BIM treatment results in the converse. Exploiting this observation, a S-Ax3 mutation targeting known MAPK and PKC sites aligned from Cx43, was generated. However, channels are able to reside in the sub-conductance state and cells are anti-proliferative. Four additional serine to alanine mutations at putative phosphorylation sites (>90%) were made to generate an S7A mutation and did not dispel the growth suppressive effect of Cx37. A phosphomimetic S7D mutation appears to induce cell death. Based on these data, it appears that substate behavior regulated by the CT is indicative growth suppression by Cx37.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplineNutritional Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.