An Intracellular Multi-Effector Complex Mediates Somatostatin Receptor 1 Activation of Phospho-Tyrosine Phosphatase η
| Autor: | Alessandro Massa, Alessandra Pattarozzi, Tullio Florio, Alfredo Fusco, Jean-Pierre Estève, Sara Arena, Christiane Susini, Rodolfo Iuliano |
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| Přispěvatelé: | Arena, S., Pattarozzi, A., Massa, A., Esteve, J. P., Iuliano, R., Fusco, Alfredo, Susini, C., Florio, T. . |
| Rok vydání: | 2007 |
| Předmět: |
Protein Tyrosine Phosphatase
Non-Receptor Type 11 CHO Cells Protein tyrosine phosphatase Biology Cricetulus Cytosol Endocrinology Cricetinae Animals Somatostatin receptor 1 Receptors Somatostatin Tyrosine Molecular Biology Genes Dominant Intracellular Signaling Peptides and Proteins General Medicine Janus Kinase 2 PTPeta Rats Cell biology Enzyme Activation src-Family Kinases Pertussis Toxin Biochemistry somatostatin receptor 1 Phosphorylation Protein Tyrosine Phosphatases Janus kinase Tyrosine kinase Intracellular Protein Binding Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Molecular Endocrinology. 21:229-246 |
| ISSN: | 1944-9917 0888-8809 |
| DOI: | 10.1210/me.2006-0081 |
| Popis: | The receptor-like phosphotyrosine phosphatase eta (PTPeta) is an important intracellular effector of the cytostatic action of SST. Here we characterize, in Chinese hamster ovary-k1 cells, the intracellular pathway that from somatostatin receptor 1 (SSTR1), leads to the activation of PTPeta and that involves, in a multimeric complex and sequential activation, the tyrosine kinases Janus kinase (JAK) 2 and Src, and the cytosolic phosphotyrosine phosphatase SHP-2. We show that inhibitors of JAK2 and Src and dominant-negative mutants of SHP-2 and Src abolished the SSTR1-mediated PTPeta activation, suggesting that all these effectors participate in the activation of PTPeta. In basal conditions, JAK2 forms a multimeric complex with SHP-2, Src and PTPeta. In response to SST, JAK2 is activated in a G protein-dependent manner, dissociates from and phosphorylates SHP-2, increasing its activity. Subsequently, SHP-2 dissociates from Src, dephosphorylates the Src inhibitory tyrosine-529, and causes an autocatalytical increase of the phosphorylation of Src tyrosine 418, located inside its kinase activation loop. Active Src, in turn, controls the activity of PTPeta, via a direct interaction and phosphorylation of the phosphatase. These data for the first time depict an intracellular pathway involving a precise sequence of interactions and cross-activation among tyrosine phosphatases and kinases acting upstream of PTPeta. In particular the sequential activation of JAK2, SHP-2, and Src conveys the molecular signaling from SSTR1 to the activation of this phosphatase that is responsible for the final biological effects of SST. |
| Databáze: | OpenAIRE |
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