Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons.
The hyaluronan (HA)-binding function (lectin function) of the leukocyte homing receptor, CD44, is tightly regulated. Herein we address possible mechanisms that regulate CD44 isoform-specific HA binding. Binding studies with melanoma transfectants expressing CD44H, CD44E, or with soluble immunoglobul...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
1995
|
| _version_ | 1797051375375351808 |
|---|---|
| author | Bennett, K Modrell, B Greenfield, B Bartolazzi, A Stamenkovic, I Peach, R Jackson, D Spring, F Aruffo, A |
| author_facet | Bennett, K Modrell, B Greenfield, B Bartolazzi, A Stamenkovic, I Peach, R Jackson, D Spring, F Aruffo, A |
| author_sort | Bennett, K |
| collection | OXFORD |
| description | The hyaluronan (HA)-binding function (lectin function) of the leukocyte homing receptor, CD44, is tightly regulated. Herein we address possible mechanisms that regulate CD44 isoform-specific HA binding. Binding studies with melanoma transfectants expressing CD44H, CD44E, or with soluble immunoglobulin fusions of CD44H and CD44E (CD44H-Rg, CD44E-Rg) showed that although both CD44 isoforms can bind HA, CD44H binds HA more efficiently than CD44E. Using CD44-Rg fusion proteins we show that the variably spliced exons in CD44E, V8-V10, specifically reduce the lectin function of CD44, while replacement of V8-V10 by an ICAM-1 immunoglobulin domain restores binding to a level comparable to that of CD44H. Conversely, CD44 bound HA very weakly when exons V8-V10 were replaced with a CD34 mucin domain, which is heavily modified by O-linked glycans. Production of CD44E-Rg or incubation of CD44E-expressing transfectants in the presence of an O-linked glycosylation inhibitor restored HA binding to CD44H-Rg and to cell surface CD44H levels, respectively. We conclude that differential splicing provides a regulatory mechanism for CD44 lectin function and that this effect is due in part to O-linked carbohydrate moieties which are added to the Ser/Thr rich regions encoded by the variably spliced CD44 exons. Alternative splicing resulting in changes in protein glycosylation provide a novel mechanism for the regulation of lectin activity. |
| first_indexed | 2024-03-06T18:18:38Z |
| format | Journal article |
| id | oxford-uuid:0582ab42-4668-4d92-8996-efb35433377d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:18:38Z |
| publishDate | 1995 |
| record_format | dspace |
| spelling | oxford-uuid:0582ab42-4668-4d92-8996-efb35433377d2022-03-26T08:57:35ZRegulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0582ab42-4668-4d92-8996-efb35433377dEnglishSymplectic Elements at Oxford1995Bennett, KModrell, BGreenfield, BBartolazzi, AStamenkovic, IPeach, RJackson, DSpring, FAruffo, AThe hyaluronan (HA)-binding function (lectin function) of the leukocyte homing receptor, CD44, is tightly regulated. Herein we address possible mechanisms that regulate CD44 isoform-specific HA binding. Binding studies with melanoma transfectants expressing CD44H, CD44E, or with soluble immunoglobulin fusions of CD44H and CD44E (CD44H-Rg, CD44E-Rg) showed that although both CD44 isoforms can bind HA, CD44H binds HA more efficiently than CD44E. Using CD44-Rg fusion proteins we show that the variably spliced exons in CD44E, V8-V10, specifically reduce the lectin function of CD44, while replacement of V8-V10 by an ICAM-1 immunoglobulin domain restores binding to a level comparable to that of CD44H. Conversely, CD44 bound HA very weakly when exons V8-V10 were replaced with a CD34 mucin domain, which is heavily modified by O-linked glycans. Production of CD44E-Rg or incubation of CD44E-expressing transfectants in the presence of an O-linked glycosylation inhibitor restored HA binding to CD44H-Rg and to cell surface CD44H levels, respectively. We conclude that differential splicing provides a regulatory mechanism for CD44 lectin function and that this effect is due in part to O-linked carbohydrate moieties which are added to the Ser/Thr rich regions encoded by the variably spliced CD44 exons. Alternative splicing resulting in changes in protein glycosylation provide a novel mechanism for the regulation of lectin activity. |
| spellingShingle | Bennett, K Modrell, B Greenfield, B Bartolazzi, A Stamenkovic, I Peach, R Jackson, D Spring, F Aruffo, A Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons. |
| title | Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons. |
| title_full | Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons. |
| title_fullStr | Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons. |
| title_full_unstemmed | Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons. |
| title_short | Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons. |
| title_sort | regulation of cd44 binding to hyaluronan by glycosylation of variably spliced exons |
| work_keys_str_mv | AT bennettk regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons AT modrellb regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons AT greenfieldb regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons AT bartolazzia regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons AT stamenkovici regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons AT peachr regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons AT jacksond regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons AT springf regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons AT aruffoa regulationofcd44bindingtohyaluronanbyglycosylationofvariablysplicedexons |