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Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Hu, Junjie Hubbard, Stevan R. |
| Copyright Year | 2006 |
| Abstract | SH2-B, APS, and Lnk constitute a family of adapter proteins that modulate signaling by protein tyrosine kinases. These adapters contain an N-terminal dimerization region, a pleckstrin homology domain, and a C-terminal Src homology-2 (SH2) domain. SH2-B is recruited via its SH2 domain to various protein tyrosine kinases, including Janus kinase-2 (Jak2) and the insulin receptor. Here, we present the crystal structure at 2.35 A resolution of the SH2 domain of SH2-B in complex with a phosphopeptide representing the SH2-B recruitment site in Jak2 (pTyr813). The structure reveals a canonical SH2 domain-phosphopeptide binding mode, but with specific recognition of a glutamate at the +1 position relative to phosphotyrosine, in addition to recognition of a hydrophobic residue at the +3 position. Biochemical studies of SH2-B and APS demonstrate that, although the SH2 domains of these two adapter proteins share 79% sequence identity, the SH2-B SH2 domain binds preferentially to Jak2, whereas the APS SH2 domain has higher affinity for the insulin receptor. This differential specificity is attributable to the difference in the oligomeric states of the two SH2 domains: monomeric for SH2-B and dimeric for APS. |
| Starting Page | 69 |
| Ending Page | 79 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://hu-lab.org/files/2017/03/download7.pdf |
| PubMed reference number | 16824542v1 |
| Volume Number | 361 |
| Issue Number | 1 |
| Journal | Journal of molecular biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Dimerization Glutamic Acid Homologous Gene Phosphotyrosine Pleckstrin Homology Domains Protein Tyrosine Kinase SH2 Domain SH2B1 wt Allele |
| Content Type | Text |
| Resource Type | Article |
