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Other Signaling Molecules (other + signaling_molecule)
Selected AbstractsInduction of neurogenin-1 expression by sonic hedgehog: Its role in development of trigeminal sensory neuronsDEVELOPMENTAL DYNAMICS, Issue 4 2003Mitsunori Ota Abstract We have examined the roles of signaling molecules in the mechanisms underlying the induction of neurogenin (ngn)-1 expression. ngn-1 is a basic helix-loop-helix (bHLH) transcription factor, which is essential for the specification of trigeminal sensory neurons. Semiquantitative reverse transcriptase-polymerase chain reaction using cranial explants in organ cultures showed that sonic hedgehog (Shh) promotes ngn-1 expression. This promoting activity was not observed in other signaling molecules examined. The promotion of ngn-1 expression by Shh, furthermore, was inhibited by cyclopamine, a specific inhibitor of Shh signaling. Shh did not affect the expression of ngn-2, a bHLH transcription factor that plays an important role in the specification of epibranchial placode-derived sensory neurons. The expression levels of ngn-1 and ngn-2 decreased after fibroblast growth factor-2 treatment. These results suggest that Shh induces ngn-1 expression specifically and that expression of ngn-1 and ngn-2 is regulated by different mechanisms. The induction of ngn-1 expression by Shh suggests that this signaling molecule participates in the specification of trigeminal sensory neurons. We therefore examined the effect of Shh on the development of these neurons. Immunostaining using anti,ngn-1 demonstrated that Shh promotes ngn-1 expression in trigeminal neural crest cells. Trigeminal neural crest cells are derived from the posterior mesencephalon and the most-anterior rhombencephalon, and they contain a subset of precursors of trigeminal sensory neurons. Moreover, a subpopulation of trigeminal neural crest cells expressed the Shh receptor Patched. The number of cells that express Brn3a, a POU-domain transcription factor that plays an important role in differentiation of sensory neurons, also increased with Shh treatment. Our data suggest that Shh signaling is involved in the specification of trigeminal sensory neurons through the induction of ngn-1 expression. Furthermore, Shh promotes the differentiation of neural crest cells into trigeminal sensory neurons. Developmental Dynamics 227:554,551, 2003. © 2003 Wiley-Liss, Inc. [source] Dok protein family members are involved in signaling mediated by the type 1 Fc, receptorEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2003Jakub Abramson Abstract Aggregation of type 1 Fc, receptors (Fc,RI) on mast cells activates a biochemical cascade that culminates in secretion of inflammatory mediators, as well as in changes of cell morphology and adhesion properties. Some of the intracellular components involved in the early coupling events are still unidentified. Here we show that two adaptor proteins, downstream of tyrosine kinases (Dok)-1 and Dok-2, are involved in the Fc,RI coupling cascade in the rat mucosal-type mast cells of the RBL-2H3 line. Dok-1 is found to be constitutively associated with the Fc,RI, even in untreated cells, and this interaction is not affected by this receptor's aggregation. Both Dok forms undergo a fast and relatively long-term tyrosyl-phosphorylation. This modification of Dok-1 increases its association with RasGAP, suggesting that it is modulating Ras activity. Indeed, we further found that Fc,RI-mediated Ras/Raf1/Erk signaling as well as the de novo synthesis of TNF-, are markedly reduced in cells overexpressing Dok-1. Moreover, Fc,RI clustering causes both Dok-1 and Dok-2 to become docking sites for other signaling molecules including Nck, CrkL and Cas. The latter proteins have been implicated particularly in regulation of the actin-cytoskeletal reorganization. Hence Dok-1/Dok-2 may also be involved in the Fc,RI-stimulated processes of cytoskeleton rearrangement required for cell adhesion, membrane ruffling and exocytosis. [source] Association of neuronal nitric oxide synthase (nNOS) with ,1-syntrophin at the sarcolemmaMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2001Yuko Miyagoe-Suzuki Abstract ,1-syntrophin is a PDZ-containing dystrophin-associated protein, expressed predominantly in striated muscle and brain. ,1-syntrophin null mice generated by gene targeting technique showed no overt muscular dystrophic phenotype. Though other dystrophin-associated proteins were localized at the sarcolemma, neuronal nitric oxide synthase (nNOS) was selectively lost from the membrane fraction but remained in the cytoplasm. Thus, the ,1-syntrophin null mice are useful in the elucidation of the functional importance of nNOS targeting at the sarcolemma. In addition, the mice would facilitate identification of other signaling molecules, which are targeted to dystrophin complex via interaction with ,1-syntrophin. Microsc. Res. Tech. 55:164,170, 2001. © 2001 Wiley-Liss, Inc. [source] Prostaglandin E2 induces vascular endothelial growth factor secretion in prostate cancer cells through EP2 receptor-mediated cAMP pathwayMOLECULAR CARCINOGENESIS, Issue 11 2007Xingya Wang Abstract Prostaglandin E2 (PGE2) has been shown to induce expression of vascular endothelial growth factor (VEGF) and other signaling molecules in several cancers. PGE2 elicits its functions though four G-protein coupled membrane receptors (EP1,4). In this study, we investigated the role of EP receptors in PGE2 -induced molecular events in prostate cancer cells. qRT-PCR analysis revealed that PC-3 cells express a substantially higher level of EP2 and moderately higher EP4 than DU145 and LNCaP cells. LNCaP cells had virtually no detectable EP2 mRNA. EP1 and EP3 mRNAs were not detected in these cells. Treatment of prostate cancer cells with PGE2 (1 nM,10 µM) increased both VEGF secretion and cyclic adenosine monophosphate (cAMP) production. Levels of induction in PC-3 cells were greater than in DU145 and LNCaP cells. The selective EP2 agonist CAY10399 also significantly increased VEGF secretion and cAMP production in PC-3 cells, but not in DU145 and LNCaP cells. Moreover, PGE2 and CAY10399 increased mitogen activated protein kinase/extracellular signal regulated kinase (MAPK/Erk) and Akt phosphorylation in PC-3 and DU145 cells, but not in LNCaP cells. However, neither the MAPK/Erk inhibitor U0126 nor the PI3K/Akt inhibitor LY294002 abolished PGE2 -induced VEGF secretion in PC-3 cells. We further demonstrated that the adenylate cyclase activator forskolin and the cAMP anologue 8-bromo-cAMP mimicked the effects of PGE2 on VEGF secretion in PC-3 cells. Meanwhile, the adenylate cyclase inhibitor 2,5,-dideoxyadenosine, at concentrations that inhibited PGE2 -induced cAMP, significantly blocked PGE2 -induced VEGF secretion in PC-3 cells. We conclude that PGE2 -induced VEGF secretion in prostate cancer cells is mediated through EP2-, and possibly EP4-, dependent cAMP signaling pathways. © 2007 Wiley-Liss, Inc. [source] Insulin-like growth factor-I receptor signal transduction and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathwayBIOFACTORS, Issue 1 2009Eddy Himpe Abstract The insulin-like growth factor IGF-I is an important fetal and postnatal growth factor, which is also involved in tissue homeostasis via regulation of proliferation, differentiation, and cell survival. To understand the role of IGF-I in the pathophysiology of a variety of disorders, including growth disorders, cancer, and neurodegenerative diseases, a detailed knowledge of IGF-I signal transduction is required. This knowledge may also contribute to the development of new therapies directed at the IGF-I receptor or other signaling molecules. In this review, we will address IGF-I receptor signaling through the JAK/STAT pathway in IGF-I signaling and the role of cytokine-induced inhibitors of signaling (CIS) and suppressors of cytokine signaling (SOCS). It appears that, in addition to the canonical IGF-I signaling pathways through extracellular-regulated kinase (ERK) and phosphatidylinositol-3 kinase (PI3K)-Akt, IGF-I also signals through the JAK/STAT pathway. Activation of this pathway may lead to induction of SOCS molecules, well-known feedback inhibitors of the JAK/STAT pathway, which also suppress of IGF-I-induced JAK/STAT signaling. Furthermore, other IGF-I-induced signaling pathways may also be modulated by SOCS. It is conceivable that the effect of these classical inhibitors of cytokine signaling directly affect IGF-I receptor signaling, because they are able to associate to the intracellular part of the IGF-I receptor. These observations indicate that CIS and SOCS molecules are key to cross-talk between IGF-I receptor signaling and signaling through receptors belonging to the hematopoietic/cytokine receptor superfamily. Theoretically, dysregulation of CIS or SOCS may affect IGF-I-mediated effects on body growth, cell differentiation, proliferation, and cell survival. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source] | |||||||||||||