Sphingosine kinase
From Proteopedia
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The '''Sphingosine Kinase Type 1 (SphK1)''' structure reveals a two domain '''alpha-beta''' architecture. <ref name="wang">PMID:23602659</ref> The '''catalytic site''' (used in converting sphingosine to S1P-see below in "function" section for more details) is in a '''hydrophobic''' cleft, located between the two domains. <ref name="wang">PMID:23602659</ref> This hydrophobic cleft is an '''ideal binding pocket''' for a '''hydrophobic lipid''', like '''sphingosine''' (an '''18-carbon''' amino alcohol with an '''unsaturated''' '''hydrocarbon''' chain). <ref name="wang">PMID:23602659</ref> | The '''Sphingosine Kinase Type 1 (SphK1)''' structure reveals a two domain '''alpha-beta''' architecture. <ref name="wang">PMID:23602659</ref> The '''catalytic site''' (used in converting sphingosine to S1P-see below in "function" section for more details) is in a '''hydrophobic''' cleft, located between the two domains. <ref name="wang">PMID:23602659</ref> This hydrophobic cleft is an '''ideal binding pocket''' for a '''hydrophobic lipid''', like '''sphingosine''' (an '''18-carbon''' amino alcohol with an '''unsaturated''' '''hydrocarbon''' chain). <ref name="wang">PMID:23602659</ref> | ||
| - | == | + | == Sphingolipids == |
'''Sphingolipids''' are a class of lipids, containing a sphingosine base moiety, essential for eukaryotic cell membrane structure and function. <ref name="futerman">PMID:15289826</ref> Importantly, sphingolipids can additionally act as critical signaling molecules used in many eukaryotic homeostatic cellular processes, such as inflammation, proliferation, apoptosis, cell migration, and '''pathogen defense'''. <ref name="futerman">PMID:15289826</ref> Because of this, it is critical for sphingolipids and their metabolizing enzymes to exist in a delicate homeostatic balance within the eukaryotic cell system. | '''Sphingolipids''' are a class of lipids, containing a sphingosine base moiety, essential for eukaryotic cell membrane structure and function. <ref name="futerman">PMID:15289826</ref> Importantly, sphingolipids can additionally act as critical signaling molecules used in many eukaryotic homeostatic cellular processes, such as inflammation, proliferation, apoptosis, cell migration, and '''pathogen defense'''. <ref name="futerman">PMID:15289826</ref> Because of this, it is critical for sphingolipids and their metabolizing enzymes to exist in a delicate homeostatic balance within the eukaryotic cell system. | ||
'''Sphingosine-1-Phosphate (S1P)''', a lipid within the sphingolipid class, is an important signaling molecule that can participate in intracellular and extracellular signaling. <ref name="futerman">PMID:15289826</ref> <ref name="Spiegel">PMID:12728273</ref> If meant to be an intracellular signaling molecule, S1P is important for cell survival, growth, and overall cell function.<ref name="Spiegel">PMID:12728273</ref> Alternatively, if S1P is meant to be an extracellular signaling molecule, later binding to one of five different S1P G-Protein Coupled Receptors on the same or different cell type, it is used to activate many signaling cascades important for cell response. <ref name="Spiegel">PMID:12728273</ref> One '''important function of S1P''', whether its fate serves intracellularly or extracellularly, is '''eliciting the immune response (i.e. lymphocyte trafficking)''', especially as a mechanism in '''pathogen defense'''. <ref name="Spiegel">PMID:12728273</ref> | '''Sphingosine-1-Phosphate (S1P)''', a lipid within the sphingolipid class, is an important signaling molecule that can participate in intracellular and extracellular signaling. <ref name="futerman">PMID:15289826</ref> <ref name="Spiegel">PMID:12728273</ref> If meant to be an intracellular signaling molecule, S1P is important for cell survival, growth, and overall cell function.<ref name="Spiegel">PMID:12728273</ref> Alternatively, if S1P is meant to be an extracellular signaling molecule, later binding to one of five different S1P G-Protein Coupled Receptors on the same or different cell type, it is used to activate many signaling cascades important for cell response. <ref name="Spiegel">PMID:12728273</ref> One '''important function of S1P''', whether its fate serves intracellularly or extracellularly, is '''eliciting the immune response (i.e. lymphocyte trafficking)''', especially as a mechanism in '''pathogen defense'''. <ref name="Spiegel">PMID:12728273</ref> | ||
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| + | == Sphingosine Kinase (SphK1 and SphK2)== | ||
'''Sphingosine Kinase''', existing in two isoenzyme forms, SphK1 and SphK2, '''creates S1P via the phosphorylation of sphingosine''', the base moiety of all sphingolipids. <ref name="Spiegel">PMID:12728273</ref> SphK1 is a central enzyme controlling the levels of S1P within the eukaryotic cell, and thus, is an important regulator of diverse cellular functions. <ref name="wang">PMID:23602659</ref> | '''Sphingosine Kinase''', existing in two isoenzyme forms, SphK1 and SphK2, '''creates S1P via the phosphorylation of sphingosine''', the base moiety of all sphingolipids. <ref name="Spiegel">PMID:12728273</ref> SphK1 is a central enzyme controlling the levels of S1P within the eukaryotic cell, and thus, is an important regulator of diverse cellular functions. <ref name="wang">PMID:23602659</ref> | ||
Revision as of 19:02, 26 April 2022
Structure Overview
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References
- ↑ 1.0 1.1 1.2 1.3 Wang Z, Min X, Xiao SH, Johnstone S, Romanow W, Meininger D, Xu H, Liu J, Dai J, An S, Thibault S, Walker N. Molecular Basis of Sphingosine Kinase 1 Substrate Recognition and Catalysis. Structure. 2013 Apr 16. pii: S0969-2126(13)00086-5. doi:, 10.1016/j.str.2013.02.025. PMID:23602659 doi:http://dx.doi.org/10.1016/j.str.2013.02.025
- ↑ 2.0 2.1 2.2 Futerman AH, Hannun YA. The complex life of simple sphingolipids. EMBO Rep. 2004 Aug;5(8):777-82. doi: 10.1038/sj.embor.7400208. PMID:15289826 doi:http://dx.doi.org/10.1038/sj.embor.7400208
- ↑ 3.0 3.1 3.2 3.3 3.4 Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol. 2003 May;4(5):397-407. doi: 10.1038/nrm1103. PMID:12728273 doi:http://dx.doi.org/10.1038/nrm1103
