The N-linked glycans attached to cytokine receptors modulate signal transduction by interacting with galectin-3 and generating a cell surface lattice. This opposes constitutive endocytosis and reduces the thresholds for cytokine signaling. The preferred ligands for galectin-3 are the poly-N-acetyl lactosaminylated tetra-antennary glycans which are synthesized by Mgat 5 and are present at high levels in tumor cells. A null mutation in Mgat 5 inhibits lattice formation and cancer progression in cells with an oncogenic background. GlcNAc feeding reestablishes lattice formation, cytokine signaling and tumorigenesis.
A MALDI-TOF analysis was employed to identify the N-glycans involved in modulating signal transduction in wild type and null Mgat 5 cells grown with different GlcNAc supplements. Native N-glycan profiling showed alterations in N glycosylation generated by GlcNAc supplements through stimulation of hexosamine pathway. After methylation the tetra-antennary and poly-N-acetyl lactosaminylated glycans were identified only in Mgat 5 wild type cells either supplemented or not with GlcNAc. These structures were absent from the signaling deficient Mgat 5 null cells. Although lattice formation and tumor progression are reestablished after GlcNAc feeding, the preferred galectin-3 ligands were absent from Mgat 5 null cells. Collision Induced Dissociation in a MALDI-IT-TOF instrument was used for N-glycan structural determination. For monitoring the alterations in N-glycosylation, null and wild type Mgat 5 cells were grown in medium supplemented with increasing GlcNAc concentrations. The N-glycans were extracted and subjected to neuraminic acid release to facilitate quantitative estimation. Oligosaccharide profiles for the Mgat 5 wild type cells showed little variation in the high mannose glycan series and a slight increase in the relative abundances of complex type glycans. In the Mgat 5 null cells the increments in GlcNAc concentration determine increasing levels of bi- and triantennary glycans and decreasing levels of high mannose glycans. These suggest that present in a higher number the glycans with lower LacNAc multiplicity are able to establish lattice interactions with adequate avidity to stimulate cytokine signaling and tumor progression in a Mgat 5 null background.
","abstract_html":"<p>The N-linked glycans attached to cytokine receptors modulate signal transduction by interacting with galectin-3 and generating a cell surface lattice. This opposes constitutive endocytosis and reduces the thresholds for cytokine signaling. The preferred ligands for galectin-3 are the poly-N-acetyl lactosaminylated tetra-antennary glycans which are synthesized by Mgat 5 and are present at high levels in tumor cells. A null mutation in Mgat 5 inhibits lattice formation and cancer progression in cells with an oncogenic background. GlcNAc feeding reestablishes lattice formation, cytokine signaling and tumorigenesis.</p><p>A MALDI-TOF analysis was employed to identify the N-glycans involved in modulating signal transduction in wild type and null Mgat 5 cells grown with different GlcNAc supplements. Native N-glycan profiling showed alterations in N glycosylation generated by GlcNAc supplements through stimulation of hexosamine pathway. After methylation the tetra-antennary and poly-N-acetyl lactosaminylated glycans were identified only in Mgat 5 wild type cells either supplemented or not with GlcNAc. These structures were absent from the signaling deficient Mgat 5 null cells. Although lattice formation and tumor progression are reestablished after GlcNAc feeding, the preferred galectin-3 ligands were absent from Mgat 5 null cells. Collision Induced Dissociation in a MALDI-IT-TOF instrument was used for N-glycan structural determination. For monitoring the alterations in N-glycosylation, null and wild type Mgat 5 cells were grown in medium supplemented with increasing GlcNAc concentrations. The N-glycans were extracted and subjected to neuraminic acid release to facilitate quantitative estimation. Oligosaccharide profiles for the Mgat 5 wild type cells showed little variation in the high mannose glycan series and a slight increase in the relative abundances of complex type glycans. In the Mgat 5 null cells the increments in GlcNAc concentration determine increasing levels of bi- and triantennary glycans and decreasing levels of high mannose glycans. These suggest that present in a higher number the glycans with lower LacNAc multiplicity are able to establish lattice interactions with adequate avidity to stimulate cytokine signaling and tumor progression in a Mgat 5 null background.</p>","abstract_has_math":false,"creators":["Silvescu, Cristina Ileana"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Vernon Reinhold"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-01-01T08:00:00Z","date_published":"2006-01-01T08:00:00Z","updated_at":"2026-07-24T05:22:19Z","subjects":["Biology","Genetics","Chemistry","Biochemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholars.unh.edu/dissertation/329","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Vernon Reinhold"]},{"key":"dc:creator","label":"Author","values":["Silvescu, Cristina Ileana"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Genetics","Chemistry","Biochemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholars.unh.edu/dissertation/329"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The N-linked glycans attached to cytokine receptors modulate signal transduction by interacting with galectin-3 and generating a cell surface lattice. This opposes constitutive endocytosis and reduces the thresholds for cytokine signaling. The preferred ligands for galectin-3 are the poly-N-acetyl lactosaminylated tetra-antennary glycans which are synthesized by Mgat 5 and are present at high levels in tumor cells. A null mutation in Mgat 5 inhibits lattice formation and cancer progression in cells with an oncogenic background. GlcNAc feeding reestablishes lattice formation, cytokine signaling and tumorigenesis.
A MALDI-TOF analysis was employed to identify the N-glycans involved in modulating signal transduction in wild type and null Mgat 5 cells grown with different GlcNAc supplements. Native N-glycan profiling showed alterations in N glycosylation generated by GlcNAc supplements through stimulation of hexosamine pathway. After methylation the tetra-antennary and poly-N-acetyl lactosaminylated glycans were identified only in Mgat 5 wild type cells either supplemented or not with GlcNAc. These structures were absent from the signaling deficient Mgat 5 null cells. Although lattice formation and tumor progression are reestablished after GlcNAc feeding, the preferred galectin-3 ligands were absent from Mgat 5 null cells. Collision Induced Dissociation in a MALDI-IT-TOF instrument was used for N-glycan structural determination. For monitoring the alterations in N-glycosylation, null and wild type Mgat 5 cells were grown in medium supplemented with increasing GlcNAc concentrations. The N-glycans were extracted and subjected to neuraminic acid release to facilitate quantitative estimation. Oligosaccharide profiles for the Mgat 5 wild type cells showed little variation in the high mannose glycan series and a slight increase in the relative abundances of complex type glycans. In the Mgat 5 null cells the increments in GlcNAc concentration determine increasing levels of bi- and triantennary glycans and decreasing levels of high mannose glycans. These suggest that present in a higher number the glycans with lower LacNAc multiplicity are able to establish lattice interactions with adequate avidity to stimulate cytokine signaling and tumor progression in a Mgat 5 null background.
"]},{"key":"dc:title","label":"Title","values":["Structural analysis of cytokine signaling modulators"]}]}],"canonical_facts":{"dc:contributor":["Vernon Reinhold"],"dc:creator":["Silvescu, Cristina Ileana"],"dc:description.abstract":["The N-linked glycans attached to cytokine receptors modulate signal transduction by interacting with galectin-3 and generating a cell surface lattice. This opposes constitutive endocytosis and reduces the thresholds for cytokine signaling. The preferred ligands for galectin-3 are the poly-N-acetyl lactosaminylated tetra-antennary glycans which are synthesized by Mgat 5 and are present at high levels in tumor cells. A null mutation in Mgat 5 inhibits lattice formation and cancer progression in cells with an oncogenic background. GlcNAc feeding reestablishes lattice formation, cytokine signaling and tumorigenesis.
A MALDI-TOF analysis was employed to identify the N-glycans involved in modulating signal transduction in wild type and null Mgat 5 cells grown with different GlcNAc supplements. Native N-glycan profiling showed alterations in N glycosylation generated by GlcNAc supplements through stimulation of hexosamine pathway. After methylation the tetra-antennary and poly-N-acetyl lactosaminylated glycans were identified only in Mgat 5 wild type cells either supplemented or not with GlcNAc. These structures were absent from the signaling deficient Mgat 5 null cells. Although lattice formation and tumor progression are reestablished after GlcNAc feeding, the preferred galectin-3 ligands were absent from Mgat 5 null cells. Collision Induced Dissociation in a MALDI-IT-TOF instrument was used for N-glycan structural determination. For monitoring the alterations in N-glycosylation, null and wild type Mgat 5 cells were grown in medium supplemented with increasing GlcNAc concentrations. The N-glycans were extracted and subjected to neuraminic acid release to facilitate quantitative estimation. Oligosaccharide profiles for the Mgat 5 wild type cells showed little variation in the high mannose glycan series and a slight increase in the relative abundances of complex type glycans. In the Mgat 5 null cells the increments in GlcNAc concentration determine increasing levels of bi- and triantennary glycans and decreasing levels of high mannose glycans. These suggest that present in a higher number the glycans with lower LacNAc multiplicity are able to establish lattice interactions with adequate avidity to stimulate cytokine signaling and tumor progression in a Mgat 5 null background.
"],"dc:identifier":["https://scholars.unh.edu/dissertation/329"],"dc:subject":["Biology","Genetics","Chemistry","Biochemistry"],"dc:title":["Structural analysis of cytokine signaling modulators"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:22:19Z"}