Somatostatin/somatostatin receptor signalling: phosphotyrosine phosphatases.
Activation of phosphotyrosine phosphatases (PTPs) by somatostatin receptor (SSTR) represents one of the main intracellular mechanisms involved in the antiproliferative effect of somatostatin (SST) and analogues. Since their molecular cloning, the role of PTPs is emerging as a major regulator of different cell functions including cell proliferation, differentiation, cell to cell interactions, cell matrix adhesion and cell migration. It was demonstrated that PTPs possess high substrate specificity and their activity is tightly regulated. Importantly, different G protein-coupled receptors transduce their biological activities through PTPs. PTPs were identified as down-stream effectors of SSTRs to transduce antiproliferative signals, and so far, three family members (SHP-1, SHP-2 and DEP-1/PTPeta) have been identified as selective SSTR intracellular effectors. Here, the molecular mechanisms leading SSTRs to regulate PTP activity are discussed, focusing on recent data showing a close interplay between PTPs and tyrosine kinases to transduce tumoral cell growth arrest following SST analogs administration.
Florio
Tullio
T
Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy. tullio.florio@unige.it
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000502:physiology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000502:physiology; D017481:Receptors, Somatostatin / Q000502:physiology*; D015398:Signal Transduction; D013004:Somatostatin / Q000502:physiology*; D013379:Substrate Specificity
D048868:Adaptor Proteins, Signal Transducing; D017481:Receptors, Somatostatin; D013004:Somatostatin; C486288:PTPRJ protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3