Huntingtin-interacting protein 1 phosphorylation by receptor tyrosine kinases
| Autor: | Anmin A. Wang, Sha Huang, Chiron W. Graves, Heather M. Ames, Alanna Coughran, Theodora S. Ross, Abigail A. Soyombo, Kristen Evaul |
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| Rok vydání: | 2013 |
| Předmět: |
Oncogene Proteins
Fusion Receptor Protein-Tyrosine Kinases Amino Acid Motifs Molecular Sequence Data Vesicular Transport Proteins Receptor tyrosine kinase Receptor Platelet-Derived Growth Factor beta chemistry.chemical_compound Mice Chlorocebus aethiops Animals Humans Epidermal growth factor receptor Amino Acid Sequence Tyrosine Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing biology Sequence Homology Amino Acid Microfilament Proteins Signal transducing adaptor protein Tyrosine phosphorylation Cell Biology Huntingtin-interacting protein 1 Articles Molecular biology DNA-Binding Proteins ErbB Receptors HEK293 Cells chemistry Amino Acid Substitution COS Cells Mutation biology.protein NIH 3T3 Cells HeLa Cells |
| Zdroj: | Molecular and cellular biology. 33(18) |
| ISSN: | 1098-5549 |
| Popis: | Huntingtin-interacting protein 1 (HIP1) binds inositol lipids, clathrin, actin, and receptor tyrosine kinases (RTKs). HIP1 is elevated in many tumors, and its expression is prognostic in prostate cancer. HIP1 overexpression increases levels of the RTK epidermal growth factor receptor (EGFR) and transforms fibroblasts. Here we report that HIP1 is tyrosine phosphorylated in the presence of EGFR and platelet-derived growth factor β receptor (PDGFβR) as well as the oncogenic derivatives EGFRvIII, HIP1/PDGFβR (H/P), and TEL/PDGFβR (T/P). We identified a four-tyrosine "HIP1 phosphorylation motif" (HPM) in the N-terminal region of HIP1 that is required for phosphorylation mediated by both EGFR and PDGFβR but not by the oncoproteins H/P and T/P. We also identified a tyrosine residue (Y152) within the HPM motif of HIP1 that inhibits HIP1 tyrosine phosphorylation. The HPM tyrosines are conserved in HIP1's only known mammalian relative, HIP1-related protein (HIP1r), and are also required for HIP1r phosphorylation. Tyrosine-to-phenylalanine point mutations in the HPM of HIP1 result in proapoptotic activity, indicating that an intact HPM may be necessary for HIP1's role in cellular survival. These data suggest that phosphorylation of HIP1 by RTKs in an N-terminal region contributes to the promotion of cellular survival. |
| Databáze: | OpenAIRE |
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