Downstream signaling molecules bind to different phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) peptides of the high affinity IgE receptor
| Autor: | Siba Bhattacharyya, Teruaki Kimura, Hidetoshi Kihara, Ettore Appella, Hiroshi Sakamoto, Reuben P. Siraganian |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Macromolecular Substances
Recombinant Fusion Proteins Molecular Sequence Data Syk environment and public health Biochemistry Cell Line src Homology Domains chemistry.chemical_compound Mice LYN Immunoreceptor tyrosine-based activation motif Animals Syk Kinase Amino Acid Sequence Phosphorylation Molecular Biology Enzyme Precursors biology Phospholipase C gamma Receptors IgE Cell Membrane Intracellular Signaling Peptides and Proteins Antibodies Monoclonal Receptor Protein-Tyrosine Kinases hemic and immune systems Tyrosine phosphorylation Cell Biology Protein-Tyrosine Kinases Fusion protein Peptide Fragments Rats Isoenzymes enzymes and coenzymes (carbohydrates) chemistry Type C Phospholipases biology.protein GRB2 biological phenomena cell phenomena and immunity Proto-oncogene tyrosine-protein kinase Src Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 271(44) |
| ISSN: | 0021-9258 |
| Popis: | The cytoplasmic tails of both the beta and gamma subunits of the high affinity IgE receptor (FcepsilonRI) contain a consensus sequence termed the immunoreceptor tyrosine-based activation motif (ITAM). This motif plays a critical role in receptor-mediated signal transduction. Synthetic peptides based on the ITAM sequences of the beta and gamma subunits of FcepsilonRI were used to investigate which proteins associate with these motifs. Tyrosine-phosphorylated beta and gamma ITAM peptides immobilized on beads precipitated Syk, Lyn, Shc, Grb2, and phospholipase C-gamma1 from lysates of rat basophilic leukemia RBL-2H3 cells. Syk was precipitated predominantly by the tyrosine-diphosphorylated gamma ITAM peptide, but much less by the diphosphorylated beta ITAM peptide or by the monophosphorylated peptides. Phospholipase C-gamma1, Shc, and Grb2 were precipitated only by the diphosphorylated beta ITAM peptide. Non-phosphorylated ITAM peptides did not precipitate these proteins. In membrane binding assays, fusion proteins containing the Src homology 2 domains of phospholipase C-gamma1, Shc, Syk, and Lyn directly bound the tyrosine-phosphorylated ITAM peptides. Although the ITAM sequences of the beta and gamma subunits of FcepsilonRI are similar, once they are tyrosine-phosphorylated they preferentially bind different downstream signaling molecules. Tyrosine phosphorylation of the ITAM of the gamma subunit recruits and activates Syk, whereas the beta subunit may be important for the Ras signaling pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|