Ceramide Signaling Pathway BioCarta

Preferred Label : Ceramide Signaling Pathway BioCarta;

NCIt related terms : Ceramide Signaling Pathway;

Alternative definition : BIOCARTA: Ceramide is a sphingosine-based lipid-signaling molecule involved in the regulation of cellular differentiation, proliferation, and apoptosis. This diagram represents some of the current understanding of the cascades that couple ceramide to specific signaling pathways. These cascades illustrate that ceramide can be a growth stimulus or proapoptotic signal. The ultimate ceramide action is determined within the context of other stimuli and by the subcellular topology of its production and is cell-type specific. There are 2 forms of sphingomyelinase, acid (acid-sphingomyelinase, A-SMase) and neutral (neutral-sphingomyelinase, N-SMase), that can produce ceramide. TNF-alpha can stimulate either form of sphingomyelinase as can other death receptors. Different domains of TNF-alpha stimulate the different SMases. N-SMase stimulation is enhanced by the receptor for activated-C kinase 1 (RACK1). The activity of each form is dependent on the local intracellular pH. In the illustration the forms are separated to reduce confusion however ceramide produced by either method can stimulate either cascade depending on the presence of specific co-factors and activators. A-SMase has been recognized as one of the required molecules to mediate proapoptotic signaling in cell death induced by a diverse array of stresses such as H2O2, Heat, UV exposure and Radiation. ROS generation in mitochondria activates caspase-3 via cooperation of cytochrome c, Aif and caspase-9 and stimulates or increases ceramide generation through A-SMase in a proapoptotic activation cycle. Caspase-3 further increases its own activation by proteolytically cleaving ceramide inhibited catalase which is an inhibitor of ROS generation. Ceramide-activated protein kinase(CARK) also known as Kinase Suppressor of RAS (KSR) activity is in some cases the switch point in the balance between proapoptotic and antiapoptotic signals and is also cell-type specific. In endothelial cells for example the activation of KSR is required for apoptosis. In contrast in epithelial cells activation of KSR is required for cell proliferation. An additional switch point is the availability of Bad in the cell. Activation of KSR leads to further mitochondrial stimulation or association with RAS and activation of the Raf1 cascade leading to proliferation or differentiation. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_ceramidePathway;

Details

Origin ID

C39026;

UMLS CUI

C1516396;

Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- Apoptosis Regulator BAX [NCIt concept]
- Apoptosis Regulator Bcl-2 [NCIt concept]
- Bcl2 Antagonist of Cell Death [NCIt concept]
- Caspase-8 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 2 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 4 [NCIt concept]
- FAS-Associated Death Domain Protein [NCIt concept]
- Kinase Suppressor of Ras 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Mitogen-Activated Protein Kinase 8 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- RAF Proto-Oncogene Serine/Threonine-Protein Kinase [NCIt concept]
- Receptor-Interacting Serine/Threonine-Protein Kinase 1 [NCIt concept]
- Sphingomyelin Phosphodiesterase [NCIt concept]
- Sphingomyelin Phosphodiesterase 2 [NCIt concept]
- TNF Receptor-Associated Factor 2 [NCIt concept]
- Transcription Factor p65 [NCIt concept]
- Tumor Necrosis Factor [NCIt concept]
- Tumor Necrosis Factor Receptor 1-Associated DEATH Domain Protein [NCIt concept]
- Tumor Necrosis Factor Receptor Superfamily Member 1A [NCIt concept]
pathway_has_gene_element
- BAD wt Allele [NCIt concept]
- BAX wt Allele [NCIt concept]
- BCL2 wt Allele [NCIt concept]
- CASP8 wt Allele [NCIt concept]
- FADD wt Allele [NCIt concept]
- KSR1 wt Allele [NCIt concept]
- MAP2K1 wt Allele [NCIt concept]
- MAP2K2 wt Allele [NCIt concept]
- MAP2K4 wt Allele [NCIt concept]
- MAP3K1 wt Allele [NCIt concept]
- MAP4K4 wt Allele [NCIt concept]
- MAPK1 wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- MAPK8 wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- RAF1 wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- RIPK1 wt Allele [NCIt concept]
- SMPD1 wt Allele [NCIt concept]
- SMPD2 wt Allele [NCIt concept]
- TNF wt Allele [NCIt concept]
- TNFRSF1A wt Allele [NCIt concept]
- TRADD wt Allele [NCIt concept]
- TRAF2 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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