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A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Arvidsson, Annette Crompton, Anne Moon Vanrenterghem, B. Wang, Dai Shu Chen, Chong S. |
| Copyright Year | 1997 |
| Abstract | Pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains are structurally related regulatory modules that are present in a variety of proteins involved in signal transduction, such as kinases, phospholipases, GTP exchange proteins, and adapter proteins. Initially these domains were shown to mediate protein-protein interactions, but more recently they were also found to bind phosphoinositides. Most studies to date have focused on binding of PH domains to phosphatidylinositol (PtdIns)-4-P and PtdIns-4,5-P2 and have not considered the lipid products of phosphoinositide 3-kinase: PtdIns-3-P, PtdIns-3,4-P2, and PtdIns-3,4,5-P3. Here we have compared the phosphoinositide specificity of six different PH domains and the Shc PTB domain using all five phosphoinositides. We show that the Bruton's tyrosine kinase PH domain binds to PtdIns-3,4, 5-P3 with higher affinity than to PtdIns-4,5-P2, PtdIns-3,4-P2 or inositol 1,3,4,5-tetrakisphosphate (Ins-1,3,4,5-P4). This selectivity is decreased by the xid mutation (R28C). Selective binding of PtdIns-3,4,5-P3 over PtdIns-4,5-P2 or PtdIns-3,4-P2 was also observed for the amino-terminal PH domain of T lymphoma invasion and metastasis protein (Tiam-1), the PH domains of Son-of-sevenless (Sos) and, to a lesser extent, the PH domain of the beta-adrenergic receptor kinase. The oxysterol binding protein and beta-spectrin PH domains bound PtdIns-3,4,5-P3 and PtdIns-4,5-P2 with similar affinities. PtdIns-3,4,5-P3 and PtdIns-4,5-P2 also bound to the PTB domain of Shc with similar affinities and lipid binding was competed with phosphotyrosine (Tyr(P)-containing peptides. These results indicate that distinct PH domains select for different phosphoinositides. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/272/35/22059.full.pdf |
| PubMed reference number | 9268346v1 |
| Volume Number | 272 |
| Issue Number | 35 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | ADRB2 gene Adrenergic Receptor Affinity Homologous Gene Inositol Lipid Binding Lymphoma Mutation Oxysterols Phosphatidylinositols Phospholipase Phosphotyrosine Binding Domain Pleckstrin Homology Domains Protein Tyrosine Kinase Receptor Protein-Tyrosine Kinases Signal Transduction beta-Adrenergic Receptor Kinases phosphatidylinositol binding protein protein interaction |
| Content Type | Text |
| Resource Type | Article |
