Mast cells stimulated by membrane-bound, but not soluble, steel factor are dependent on phospholipase C activation

Trieselmann, N. Z.; Soboloff, Jonathan; Berger, Stuart A.

doi:10.1007/s00018-003-2349-8

Cited by 24 publications

(16 citation statements)

References 48 publications

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“…While its product (S1P) has been associated with Ca 2ϩ mobilization, evidence to the contrary also exists, since inhibitors of PLC␥ effectively inhibit mast cell and basophil Ca 2ϩ responses and degranulation (44,45). It should be noted that we also found no evidence for an association of SPHK1 activity with Ca 2ϩ mobilization, since reintroduction of Lyn kinase into Lyn Ϫ/Ϫ mast cells, which restored SPHK1 activity, did not restore the calcium response in these cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Early Activation of Sphingosine Kinase in Mast Cells and Recruitment to FcεRI Are Mediated by Its Interaction with Lyn Kinase

Urtz

Olivera

Bofill-Cardona

et al. 2004

Molecular and Cellular Biology

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Sphingosine kinase has been recognized as an essential signaling molecule that mediates the intracellular conversion of sphingosine to sphingosine-1-phosphate. In mast cells, induction of sphingosine kinase and generation of sphingosine-1-phosphate have been linked to the initial rise in Ca 2؉ , released from internal stores, and to degranulation. These events either precede or are concomitant with the activation of phospholipase C-␥ and the generation of inositol trisphosphate. Here we show that sphingosine kinase type 1 (SPHK1) interacts directly with the tyrosine kinase Lyn and that this interaction leads to the recruitment of this lipid kinase to the high-affinity receptor for immunoglobulin E (FcRI). The interaction of SPHK1 with Lyn caused enhanced lipid and tyrosine kinase activity. After FcRI triggering, enhanced sphingosine kinase activity was associated with FcRI in sphingolipid-enriched rafts of mast cells. Bone marrow-derived mast cells from Lyn ؊/؊ mice, compared to syngeneic wild-type cells, were defective in the initial induction of SPHK1 activity, and the defect was overcome by retroviral Lyn expression. These findings position the activation of SPHK1 as an FcRI proximal event.In addition to the importance of sphingolipids in membrane structure, the sphingomyelin pathway with its lipid products ceramide, sphingosine (S), and S-1-phosphate (S1P) has been recognized to function in a variety of signaling events (3, 36). Many of the sphingolipids generated along this pathway are secreted and bind specific cellular receptors on a variety of cell types. On the other hand, they also function intracellularly as "second messenger molecules" similar to the various intermediates of phosphoglyceride metabolism (3, 36). Processes such as apoptosis, differentiation, and cell activation are directly regulated or fine-tuned by ceramide and its derivatives. However, in contrast to glycerolipids, the individual concentrations of various intracellular sphingolipids serve to balance cell activation and inactivation. This concept has been termed the sphingolipid rheostat (3). Specific examples include ceramide and S1P, whose relative intracellular concentration regulates apoptosis; S and S1P, which regulates immunoglobulin E-antigen (IgE-Ag) sensitivity in mast cells; and ceramide and ceramide-1-phosphate, which regulates the process of phagocytosis in macrophages (2,14,29,37,42,43). An essential cellular checkpoint in the sphingomyelin signaling pathway is S kinase (SPHK), as its product S1P is able to counteract ceramide as well as S-mediated effects in apoptosis and effector function regulation (e.g., inhibition of cytokine induction by S in mast cells). In humans, two different isoforms and several splice variants of SPHK were described and cloned (34). While activation of SPHK1 has been firmly established (e.g., after FcεRI and Fc␥RI signaling), its relationship to other known mast cell signaling molecules is still unexplored (24, 37). Recent data on Fc␥RI positioned SPHK downstream of phospholipase D, with a de...

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Section: Discussionmentioning

confidence: 99%

Early Activation of Sphingosine Kinase in Mast Cells and Recruitment to FcεRI Are Mediated by Its Interaction with Lyn Kinase

Urtz

Olivera

Bofill-Cardona

et al. 2004

Molecular and Cellular Biology

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“…It has been found that PLC-␥ can interact with tyrosine residue 730 in c-Kit, and interestingly, cell proliferation induced by membrane-bound SCF has been shown to depend on PLC-␥ association with and activation by c-Kit (85,278). Furthermore, soluble SCF was shown to be unable to activate PLC, but did in contrast activate PLD in a PI3-kinase-dependent manner (141,143).…”

Section: Phospholipases C and D Signalingmentioning

confidence: 96%

Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications

Lennartsson

Rönnstrand

2012

Physiological Reviews

679

717

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Stem cell factor (SCF) is a dimeric molecule that exerts its biological functions by binding to and activating the receptor tyrosine kinase c-Kit. Activation of c-Kit leads to its autophosphorylation and initiation of signal transduction. Signaling proteins are recruited to activated c-Kit by certain interaction domains (e.g., SH2 and PTB) that specifically bind to phosphorylated tyrosine residues in the intracellular region of c-Kit. Activation of c-Kit signaling has been found to mediate cell survival, migration, and proliferation depending on the cell type. Signaling from c-Kit is crucial for normal hematopoiesis, pigmentation, fertility, gut movement, and some aspects of the nervous system. Deregulated c-Kit kinase activity has been found in a number of pathological conditions, including cancer and allergy. The observation that gain-of-function mutations in c-Kit can promote tumor formation and progression has stimulated the development of therapeutics agents targeting this receptor, e.g., the clinically used inhibitor imatinib mesylate. Also other clinically used multiselective kinase inhibitors, for instance, sorafenib and sunitinib, have c-Kit included in their range of targets. Furthermore, loss-of-function mutations in c-Kit have been observed and shown to give rise to a condition called piebaldism. This review provides a summary of our current knowledge regarding structural and functional aspects of c-Kit signaling both under normal and pathological conditions, as well as advances in the development of low-molecular-weight molecules inhibiting c-Kit function.

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“…Also studying bone marrow mast cells, Huber et al detected a robust and sustained SCF-stimulated tyrosine phosphorylation of PLC-g2 [100]. Likewise, Triselmann et al [101] showed that stimulation of mast cells by membrane-bound, but not soluble SCF, was dependent on PLC-g activation. They also demonstrated ligand-induced tyrosine phosphorylation of PLC-g2.…”

Section: Plc-g Gmentioning

confidence: 99%

Signal transduction via the stem cell factor receptor/c-Kit

Rönnstrand

2004

CMLS, Cell. Mol. Life Sci.

388

294

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Together with its ligand, stem cell factor, the receptor tyrosine kinase c-Kit is a key controlling receptor for a number of cell types, including hematopoietic stem cells, mast cells, melanocytes and germ cells. Gain-of-function mutations in c-Kit have been described in a number of human cancers, including testicular germinomas, acute myeloid leukemia and gastrointestinal stromal tumors. Stimulation of c-Kit by its ligand leads to dimerization of receptors, activation of its intrinsic tyrosine kinase activity and phosphorylation of key tyrosine residues within the receptor. These phosphorylated tyrosine residues serve as docking sites for a number of signal transduction molecules containing Src homology 2 domains, which will thereby be recruited to the receptor and activated many times through phosphorylation by the receptor. This review discusses our current knowledge of signal transduction molecules and signal transduction pathways activated by c-Kit and how their activation can be connected to the physiological outcome of c-Kit signaling.

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Mast cells stimulated by membrane-bound, but not soluble, steel factor are dependent on phospholipase C activation

Cited by 24 publications

References 48 publications

Early Activation of Sphingosine Kinase in Mast Cells and Recruitment to FcεRI Are Mediated by Its Interaction with Lyn Kinase

Early Activation of Sphingosine Kinase in Mast Cells and Recruitment to FcεRI Are Mediated by Its Interaction with Lyn Kinase

Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications

Signal transduction via the stem cell factor receptor/c-Kit

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