Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion.
Type IIB receptor protein tyrosine phosphatases (RPTPs) are bi-functional cell surface molecules. Their ectodomains mediate stable, homophilic, cell-adhesive interactions, whereas the intracellular catalytic regions can modulate the phosphorylation state of cadherin/catenin complexes. We describe a...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2006
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| _version_ | 1797098836549697536 |
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| author | Aricescu, A Hon, W Siebold, C Lu, W Van Der Merwe, P Jones, E |
| author_facet | Aricescu, A Hon, W Siebold, C Lu, W Van Der Merwe, P Jones, E |
| author_sort | Aricescu, A |
| collection | OXFORD |
| description | Type IIB receptor protein tyrosine phosphatases (RPTPs) are bi-functional cell surface molecules. Their ectodomains mediate stable, homophilic, cell-adhesive interactions, whereas the intracellular catalytic regions can modulate the phosphorylation state of cadherin/catenin complexes. We describe a systematic investigation of the cell-adhesive properties of the extracellular region of RPTPmu, a prototypical type IIB RPTP. The crystal structure of a construct comprising its N-terminal MAM (meprin/A5/mu) and Ig domains was determined at 2.7 A resolution; this assigns the MAM fold to the jelly-roll family and reveals extensive interactions between the two domains, which form a rigid structural unit. Structure-based site-directed mutagenesis, serial domain deletions and cell-adhesion assays allowed us to identify the four N-terminal domains (MAM, Ig, fibronectin type III (FNIII)-1 and FNIII-2) as a minimal functional unit. Biophysical characterization revealed at least two independent types of homophilic interaction which, taken together, suggest that there is the potential for formation of a complex and possibly ordered array of receptor molecules at cell contact sites. |
| first_indexed | 2024-03-07T05:15:22Z |
| format | Journal article |
| id | oxford-uuid:dcfecb03-1ec3-4fe1-ab62-4c6df8436aa5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:15:22Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:dcfecb03-1ec3-4fe1-ab62-4c6df8436aa52022-03-27T09:21:47ZMolecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dcfecb03-1ec3-4fe1-ab62-4c6df8436aa5EnglishSymplectic Elements at Oxford2006Aricescu, AHon, WSiebold, CLu, WVan Der Merwe, PJones, EType IIB receptor protein tyrosine phosphatases (RPTPs) are bi-functional cell surface molecules. Their ectodomains mediate stable, homophilic, cell-adhesive interactions, whereas the intracellular catalytic regions can modulate the phosphorylation state of cadherin/catenin complexes. We describe a systematic investigation of the cell-adhesive properties of the extracellular region of RPTPmu, a prototypical type IIB RPTP. The crystal structure of a construct comprising its N-terminal MAM (meprin/A5/mu) and Ig domains was determined at 2.7 A resolution; this assigns the MAM fold to the jelly-roll family and reveals extensive interactions between the two domains, which form a rigid structural unit. Structure-based site-directed mutagenesis, serial domain deletions and cell-adhesion assays allowed us to identify the four N-terminal domains (MAM, Ig, fibronectin type III (FNIII)-1 and FNIII-2) as a minimal functional unit. Biophysical characterization revealed at least two independent types of homophilic interaction which, taken together, suggest that there is the potential for formation of a complex and possibly ordered array of receptor molecules at cell contact sites. |
| spellingShingle | Aricescu, A Hon, W Siebold, C Lu, W Van Der Merwe, P Jones, E Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. |
| title | Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. |
| title_full | Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. |
| title_fullStr | Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. |
| title_full_unstemmed | Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. |
| title_short | Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell adhesion. |
| title_sort | molecular analysis of receptor protein tyrosine phosphatase mu mediated cell adhesion |
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