S-palmitoylation is a reversible posttranslational modification that plays an important role in regulating protein localization, trafficking, and stability. Recent studies have shown that some proteins undergo extremely rapid palmitoylation/depalmitoylation cycles after cellular stimulation supporting a direct signaling role for this posttranslational modification. The work in this dissertation investigated whether β-adrenergic stimulation led to stimulus-dependent palmitoylation of downstream signaling proteins in immortalized and primary cell models. I found that β-adrenergic stimulation led to rapidly increased Gαs and Gαi palmitoylation only in primary cardiomyocytes. The kinetics of palmitoylation was temporally consistent with the downstream production of cAMP and contractile responses. I identified the plasma membrane-localized palmitoyl acyltransferase DHHC5 as an important mediator of the stimulus-dependent palmitoylation in cardiomyocytes. Knockdown of DHHC5 showed that this enzyme is necessary for palmitoylation of Gαs, Gαi, and functional responses downstream of β-adrenergic stimulation. A palmitoylation assay with purified components revealed that Gαs and Gαi are direct substrates of DHHC5. Finally, we provided evidence that the C-terminal tail of DHHC5 can be palmitoylated in response to stimulation and such modification is important for its dynamic localization in the plasma membrane. My results reveal that DHHC5 is a central regulator of signaling downstream of β-adrenergic receptors in cardiomyocytes.
","abstract_html":"<p>S-palmitoylation is a reversible posttranslational modification that plays an important role in regulating protein localization, trafficking, and stability. Recent studies have shown that some proteins undergo extremely rapid palmitoylation/depalmitoylation cycles after cellular stimulation supporting a direct signaling role for this posttranslational modification. The work in this dissertation investigated whether β-adrenergic stimulation led to stimulus-dependent palmitoylation of downstream signaling proteins in immortalized and primary cell models. I found that β-adrenergic stimulation led to rapidly increased Gαs and Gαi palmitoylation only in primary cardiomyocytes. The kinetics of palmitoylation was temporally consistent with the downstream production of cAMP and contractile responses. I identified the plasma membrane-localized palmitoyl acyltransferase DHHC5 as an important mediator of the stimulus-dependent palmitoylation in cardiomyocytes. Knockdown of DHHC5 showed that this enzyme is necessary for palmitoylation of Gαs, Gαi, and functional responses downstream of β-adrenergic stimulation. A palmitoylation assay with purified components revealed that Gαs and Gαi are direct substrates of DHHC5. Finally, we provided evidence that the C-terminal tail of DHHC5 can be palmitoylated in response to stimulation and such modification is important for its dynamic localization in the plasma membrane. My results reveal that DHHC5 is a central regulator of signaling downstream of β-adrenergic receptors in cardiomyocytes.</p>","abstract_has_math":false,"creators":["Chen, Jie","0000-0002-6222-0055
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Darren Boehning","Vasanthi Jayaraman","Ilya Levental"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-08-01T07:00:00Z","date_published":"2019-08-01T07:00:00Z","updated_at":"2026-07-24T05:49:54Z","subjects":["Palmitoylation","DHHC proteins","Beta-adrenergic signaling","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/960","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Darren Boehning","Vasanthi Jayaraman","Ilya Levental"]},{"key":"dc:creator","label":"Author","values":["Chen, Jie","0000-0002-6222-0055
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"]},{"key":"dc:title","label":"Title","values":["Dhhc5 Regulates Beta-Adrenergic Signaling In The Heart Through Palmitoylation of G Alpha Proteins"]}]}],"canonical_facts":{"dc:contributor":["Darren Boehning","Vasanthi Jayaraman","Ilya Levental"],"dc:creator":["Chen, Jie","0000-0002-6222-0055
"],"dc:date.available":["2019-08-15T07:00:00Z"],"dc:description.abstract":["S-palmitoylation is a reversible posttranslational modification that plays an important role in regulating protein localization, trafficking, and stability. Recent studies have shown that some proteins undergo extremely rapid palmitoylation/depalmitoylation cycles after cellular stimulation supporting a direct signaling role for this posttranslational modification. The work in this dissertation investigated whether β-adrenergic stimulation led to stimulus-dependent palmitoylation of downstream signaling proteins in immortalized and primary cell models. I found that β-adrenergic stimulation led to rapidly increased Gαs and Gαi palmitoylation only in primary cardiomyocytes. The kinetics of palmitoylation was temporally consistent with the downstream production of cAMP and contractile responses. I identified the plasma membrane-localized palmitoyl acyltransferase DHHC5 as an important mediator of the stimulus-dependent palmitoylation in cardiomyocytes. Knockdown of DHHC5 showed that this enzyme is necessary for palmitoylation of Gαs, Gαi, and functional responses downstream of β-adrenergic stimulation. A palmitoylation assay with purified components revealed that Gαs and Gαi are direct substrates of DHHC5. Finally, we provided evidence that the C-terminal tail of DHHC5 can be palmitoylated in response to stimulation and such modification is important for its dynamic localization in the plasma membrane. My results reveal that DHHC5 is a central regulator of signaling downstream of β-adrenergic receptors in cardiomyocytes.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/960"],"dc:subject":["Palmitoylation","DHHC proteins","Beta-adrenergic signaling","Medicine and Health Sciences"],"dc:title":["Dhhc5 Regulates Beta-Adrenergic Signaling In The Heart Through Palmitoylation of G Alpha Proteins"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:49:54Z"}