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style="overflow:visible;enable-background:new 0 0 60.0 60.0" contentStyleType="text/css" height="60.0" viewBox="0 0 60.0 60.0" preserveAspectRatio="xMidYMid meet" xmlns="http://www.w3.org/2000/svg" version="1.0"> <defs> <radialGradient id="MO_517963" gradientUnits="objectBoundingBox" spreadMethod="pad" xlink:show="other" xlink:type="simple" r="50%" cx="50%" fx="50%" fy="50%" cy="50%" xlink:actuate="onLoad"> <stop offset="0%" style="stop-color:white;stop-opacity:1;"/> <stop offset="100%" style="stop-color:#517963;stop-opacity:1;"/> </radialGradient> </defs> <path style="fill:url(#MO_517963);stroke:none;" d="M 60 42.4263 l -10.3315 -5.9498 c -7.3426 -1.6765 2.5901 -9.7445 8.9955 -7.5253 l -16.2377 -28.9512 l -5.9498 10.3315 c -1.6765 7.3426 -9.7445 -2.5901 -7.5253 -8.9955 l -28.9512 16.2377 l 10.3315 5.9498 c 7.3426 1.6765 -2.5901 9.7445 -8.9955 7.5253 l 16.2377 28.9512 l 5.9498 -10.3315 c 1.6765 -7.3426 9.7445 2.5901 7.5253 8.9955 l 28.9512 -16.2377 z" /> </svg> PMID: 15189145 Serum LPA is bound to albumin, low-density lipoproteins, or other proteins, which possibly protect LPA from rapid degradation. PMID: 15189145 Serum LPA is bound to albumin, low-density lipoproteins, or other proteins, which possibly protect LPA from rapid degradation. PMID: 15189145, 12069820 S1P in serum is bound to albumin or lipoproteins, and its concentration is estimated to be 0.5–0.8 microM in human serum and 0.2–0.4 microM in human plasma. PMID: 15189145, 12069820 S1P in serum is bound to albumin or lipoproteins, and its concentration is estimated to be 0.5–0.8 microM in human serum and 0.2–0.4 microM in human plasma. PMID: 15189145, 8922387 LPA1 (previously called VZG-1/EDG-2/mrec1.3) was the first identified, high affinity receptor for LPA. PMID: 15189145, 9600933, 11040035 LPA1 couples with three types of G proteins, Gi/o, Gq, and G12/13.. PMID: 15189145, 9600933, 11040035 LPA1 couples with three types of G proteins, Gi/o, Gq, and G12/13.. PMID: 15189145, 9600933, 11040035 LPA1 couples with three types of G proteins, Gi/o, Gq, and G12/13. indirect PMID: 15189145, 11093753 Through activation of these G proteins, LPA induces a range of cellular responses through LPA1: cell proliferation, serum-response element (SRE) activation, MAPK activation, AC inhibition, PLC activation, Ca2+ mobilization, Akt activation, and Rho activation. indirect PMID: 15189145, 11093753 Through activation of these G proteins, LPA induces a range of cellular responses through LPA1: cell proliferation, serum-response element (SRE) activation, MAPK activation, AC inhibition, PLC activation, Ca2+ mobilization, Akt activation, and Rho activation. indirect PMID: 15189145, 11093753 Through activation of these G proteins, LPA induces a range of cellular responses through LPA1: cell proliferation, serum-response element (SRE) activation, MAPK activation, AC inhibition, PLC activation, Ca2+ mobilization, Akt activation, and Rho activation. indirect PMID: 15189145, 11093753 Through activation of these G proteins, LPA induces a range of cellular responses through LPA1: cell proliferation, serum-response element (SRE) activation, MAPK activation, AC inhibition, PLC activation, Ca2+ mobilization, Akt activation, and Rho activation. PMID: 15189145, 11093753 Through activation of these G proteins, LPA induces a range of cellular responses through LPA1: cell proliferation, serum-response element (SRE) activation, MAPK activation, AC inhibition, PLC activation, Ca2+ mobilization, Akt activation, and Rho activation. PMID: 15189145 Importantly, many LPA-induced responses, which include cell proliferation, AC inhibition, PLC activation, Calcium; mobilization, JNK and Akt activation, and stress fiber formation,are absent or severely reduced in double-null MEFs. PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P1 receptor primarily couples with PTX-sensitive Gi/o proteins and mediates S1P induced MAPK activation, AC inhibition, PLC activation, Calcium mobilization, cell aggregation, Rac (and often Rho) activation, and cell migration. PMID: 15189145 S1P5 can couple with Gi/o and G12/13 and it mediates S1P induced AC inhibition. PMID: 15189145, 11264467, 11093753 As with LPA1, LPA2 couples with three types of G proteins, Gi/o, Gq, and G12/13, to mediate LPA-induced cellular signaling PMID: 15189145, 11264467, 11093753 As with LPA1, LPA2 couples with three types of G proteins, Gi/o, Gq, and G12/13, to mediate LPA-induced cellular signaling. PMID: 15189145, 11264467, 11093753 As with LPA1, LPA2 couples with three types of G proteins, Gi/o, Gq, and G12/13, to mediate LPA-induced cellular signaling indirect PMID: 15189145 Importantly, many LPA-induced responses, which include cell proliferation, AC inhibition, PLC activation, Calcium; mobilization, JNK and Akt activation, and stress fiber formation,are absent or severely reduced in double-null MEFs. indirect PMID: 15189145 Importantly, many LPA-induced responses, which include cell proliferation, AC inhibition, PLC activation, Calcium; mobilization, JNK and Akt activation, and stress fiber formation,are absent or severely reduced in double-null MEFs. indirect PMID: 15189145 Importantly, many LPA-induced responses, which include cell proliferation, AC inhibition, PLC activation, Calcium mobilization, JNK and Akt activation, and stress fiber formation,are absent or severely reduced in double-null MEFs. PMID: 15189145, 11040035 The LPA3 receptor is distinct from LPA1 and LPA2 in its ability to couple with Gi/o and Gq but not G12/13. PMID: 15189145, 11040035 The LPA3 receptor is distinct from LPA1 and LPA2 in its ability to couple with Gi/o and Gq but not G12/13. indirect PMID: 15189145, 11040035, 10488122, 10727522 LPA3 can mediate pleiotropic LPA-induced signaling that includes PLC activation, Ca2+ mobilization, AC inhibition/activation, and MAPK activation. indirect PMID: 15189145, 11040035, 10488122, 10727522 LPA3 can mediate pleiotropic LPA-induced signaling that includes PLC activation, Ca2+ mobilization, AC inhibition/activation, and MAPK activation. PMID: 15189145, 12724320 The orphan receptor, p2y9/GPR23, is a functional high-affinity LPA receptor (Kd 45 nM)that is now classified as LPA4. PMID: 15189145 S1P1 (EDG-1/LPB1) was the first identified S1P receptor that was initially isolated as an orphan GPCR in human endothelial cells, and it was later shown to encode a high-affinity (Kd 8 nM) S1P receptor. PMID: 15189145, 11583630 Akt-mediated phosphorylation of S1P1 is required for Rac activation, cortical actin assembly, and cell migration, but not for Gi/o-dependent signaling in endothelial cells. PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P1 receptor primarily couples with PTX-sensitive Gi/o proteins and mediates S1P induced MAPK activation, AC inhibition, PLC activation, Calcium mobilization, cell aggregation, Rac (and often Rho) activation, and cell migration. indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P1 receptor primarily couples with PTX-sensitive Gi/o proteins and mediates S1P induced MAPK activation, AC inhibition, PLC activation, Calcium mobilization, cell aggregation, Rac (and often Rho) activation, and cell migration. indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P1 receptor primarily couples with PTX-sensitive Gi/o proteins and mediates S1P induced MAPK activation, AC inhibition, PLC activation, Calcium mobilization, cell aggregation, Rac (and often Rho) activation, and cell migration. indirect PMID: 15189145, 11583630 Akt-mediated phosphorylation of S1P1 is required for Rac activation, cortical actin assembly, and cell migration, but not for Gi/o-dependent signaling in endothelial cells. PMID: 15189145, 11094076 S1P2 inhibits Rac activity and prevents cell migration. PMID: 15189145, 11264467 S1P2 was later identified by many groups as a high-affinity (Kd 20–27 nM) S1P receptor and it is also encoded on a single exon. PMID: 15189145, 11264467, 12069812, 12069815, 12069818 It couples with Gi/o, Gq, G12/13, and possibly Gs, and it can mediate S1P-induced cell proliferation, cell survival, cell rounding, SRE activation, MAPK activation, AC activation,PLC activation, Ca2 mobilization, and Rho activation. PMID: 15189145, 11264467, 12069812, 12069815, 12069818 It couples with Gi/o, Gq, G12/13, and possibly Gs, and it can mediate S1P-induced cell proliferation, cell survival, cell rounding, SRE activation, MAPK activation, AC activation,PLC activation, Calcium mobilization, and Rho activation. PMID: 15189145, 11264467, 12069812, 12069815, 12069818 It couples with Gi/o, Gq, G12/13, and possibly Gs, and it can mediate S1P-induced cell proliferation, cell survival, cell rounding, SRE activation, MAPK activation, AC activation,PLC activation, Ca2 mobilization, and Rho activation. indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 It couples with Gi/o, Gq, G12/13, and possibly Gs, and it can mediate S1P-induced cell proliferation, cell survival, cell rounding, SRE activation, MAPK activation, AC activation,PLC activation, Ca2 mobilization, and Rho activation. indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 It couples with Gi/o, Gq, G12/13, and possibly Gs, and it can mediate S1P-induced cell proliferation, cell survival, cell rounding, SRE activation, MAPK activation, AC activation,PLC activation, Ca2 mobilization, and Rho activation. indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 It couples with Gi/o, Gq, G12/13, and possibly Gs, and it can mediate S1P-induced cell proliferation, cell survival, cell rounding, SRE activation, MAPK activation, AC activation,PLC activation, Ca2 mobilization, and Rho activation. PMID: 15189145, 11264467 Like S1P2, S1P3 is a high-affinity (Kd 23–26 nM) S1P receptor and is encoded on a single exon. PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P3 receptor couples with Gi/o, Gq, G12/13, and possibly Gs, and it induces cell proliferation, cell survival, cell rounding, MAPK activation,SRE activation, AC activation/inhibition, PLC activation, Ca2 mobilization, Rho activation, Rac activation, and cell migration PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P3 receptor couples with Gi/o, Gq, G12/13, and possibly Gs, and it induces cell proliferation, cell survival, cell rounding, MAPK activation,SRE activation, AC activation/inhibition, PLC activation, Ca2 mobilization, Rho activation, Rac activation, and cell migration PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P3 receptor couples with Gi/o, Gq, G12/13, and possibly Gs, and it induces cell proliferation, cell survival, cell rounding, MAPK activation,SRE activation, AC activation/inhibition, PLC activation, Ca2 mobilization, Rho activation, Rac activation, and cell migration indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P3 receptor couples with Gi/o, Gq, G12/13, and possibly Gs, and it induces cell proliferation, cell survival, cell rounding, MAPK activation,SRE activation, AC activation/inhibition, PLC activation, Ca2 mobilization, Rho activation, Rac activation, and cell migration. indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P3 receptor couples with Gi/o, Gq, G12/13, and possibly Gs, and it induces cell proliferation, cell survival, cell rounding, MAPK activation,SRE activation, AC activation/inhibition, PLC activation, Ca2 mobilization, Rho activation, Rac activation, and cell migration. indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P3 receptor couples with Gi/o, Gq, G12/13, and possibly Gs, and it induces cell proliferation, cell survival, cell rounding, MAPK activation,SRE activation, AC activation/inhibition, PLC activation, Ca2 mobilization, Rho activation, Rac activation, and cell migration. indirect PMID: 15189145, 11264467, 12069812, 12069815, 12069818 The S1P3 receptor couples with Gi/o, Gq, G12/13, and possibly Gs, and it induces cell proliferation, cell survival, cell rounding, MAPK activation,SRE activation, AC activation/inhibition, PLC activation, Ca2 mobilization, Rho activation, Rac activation, and cell migration. PMID: 15189145, 11264467 It was found to encode a high-affinity (Kd 13–63 nM) receptor for S1P. PMID: 15189145, 12270137 phytosphingosine 1-phosphate (4D-hydroxysphinganine 1-phosphate) has a 50-fold higher affinity for S1P4 PMID: 15189145, 11443127, 10679247, 10753843, 12761884 S1P4 couples with Gi/o, G12/13, and possibly Gs, and it mediates S1P-induced MAPK activation, PLC activation, Ca2 mobilization, AC activation,Rho activation, cytoskeletal rearrangement. PMID: 15189145, 11443127, 10679247, 10753843, 12761884 S1P4 couples with Gi/o, G12/13, and possibly Gs, and it mediates S1P-induced MAPK activation, PLC activation, Ca2 mobilization, AC activation,Rho activation, cytoskeletal rearrangement. indirect PMID: 15189145, 11443127, 10679247, 10753843, 12761884 S1P4 couples with Gi/o, G12/13, and possibly Gs, and it mediates S1P-induced MAPK activation, PLC activation, Ca2 mobilization, AC activation,Rho activation, cytoskeletal rearrangement. indirect PMID: 15189145, 11443127, 10679247, 10753843, 12761884 S1P4 couples with Gi/o, G12/13, and possibly Gs, and it mediates S1P-induced MAPK activation, PLC activation, Ca2 mobilization, AC activation,Rho activation, cytoskeletal rearrangement. indirect PMID: 15189145, 11443127, 10679247, 10753843, 12761884 S1P4 couples with Gi/o, G12/13, and possibly Gs, and it mediates S1P-induced MAPK activation, PLC activation, Ca2 mobilization, AC activation,Rho activation, cytoskeletal rearrangement. indirect PMID: 15189145, 11443127, 10679247, 10753843, 12761884 S1P4 couples with Gi/o, G12/13, and possibly Gs, and it mediates S1P-induced MAPK activation, PLC activation, Ca2 mobilization, AC activation,Rho activation, cytoskeletal rearrangement. PMID: 15189145, 11264467 It was later found to encode a high-affinity S1P receptor (Kd 2–10 nM) PMID: 15189145 S1P5 can couple with Gi/o and G12/13 and it mediates S1P induced AC inhibition. PMID: 15189145 S1P5 can couple with Gi/o and G12/13 and it mediates S1P induced AC inhibition. PMID: 15189145, 11474113 G2A has properties of a high-affinity LPC receptor (Kd 65 nM) and low-affinity SPC receptor (Kd 230 nM). PMID: 15189145, 11474113 G2A has properties of a high-affinity LPC receptor (Kd 65 nM) and low-affinity SPC receptor (Kd 230 nM). PMID: 15189145, 10951580, 11050239 G2A appears to couple with G12/13 and mediates the activation of small GTPases (Rho, Rac, and Ras), stress fiber formation that requires G13 and Rho, and SRE activation. indirect PMID: 15189145, 10951580, 11050239 G2A appears to couple with G12/13 and mediates the activation of small GTPases (Rho, Rac, and Ras), stress fiber formation that requires G13 and Rho, and SRE activation. indirect PMID: 15189145, 10951580, 11050239 G2A appears to couple with G12/13 and mediates the activation of small GTPases (Rho, Rac, and Ras), stress fiber formation that requires G13 and Rho, and SRE activation. indirect PMID: 15189145, 10951580, 11050239 G2A appears to couple with G12/13 and mediates the activation of small GTPases (Rho, Rac, and Ras), stress fiber formation that requires G13 and Rho, and SRE activation. PMID: 15189145 It also mediates LPC-induced Ca2 mobilization and MAPK activation in a pertussis toxin (PTX)-sensitive manner, suggesting coupling to Gi/o. indirect PMID: 15189145 It also mediates LPC-induced Ca2 mobilization and MAPK activation in a pertussis toxin (PTX)-sensitive manner, suggesting coupling to Gi/o. PMID: 15189145, 12586833 G2A couples with Gq and G13 for NF-kappaB activation. indirect PMID: 15189145, 12586833 G2A couples with Gq and G13 for NF-kappaB activation. indirect PMID: 15189145, 12586833 G2A couples with Gq and G13 for NF-kappaB activation. PMID: 15189145, 12586833 G2A couples with Gq and G13 for NF-kappaB activation. PMID: 15189145, 10806476 OGR1 encode a high-affinity (Kd 33 nM) receptor for SPC. PMID: 15189145, 10806476 OGR1 appears to couple with both Gi/o and Gq, mediating SPC-induced Ca2 mobilization via Gi/o and MAPK activation via Gq. It also mediates SPC inhibition of cell proliferation. PMID: 15189145, 10806476 OGR1 appears to couple with both Gi/o and Gq, mediating SPC-induced Ca2 mobilization via Gi/o and MAPK activation via Gq. It also mediates SPC inhibition of cell proliferation. indirect PMID: 15189145, 10806476 OGR1 appears to couple with both Gi/o and Gq, mediating SPC-induced Ca2 mobilization via Gi/o and MAPK activation via Gq. It also mediates SPC inhibition of cell proliferation. PMID: 15189145, 11535583 It was later reported to encode a high-affinity receptor for SPC (Kd 36 nM) and low-affinity receptor for LPC (Kd 159 nM). PMID: 15189145, 11535583 It was later reported to encode a high-affinity receptor for SPC (Kd 36 nM) and low-affinity receptor for LPC (Kd 159 nM). PMID: 15189145, 11535583 GPR4 appears to couple (at least) with Gi/o to mediate cell proliferation, SRE activation, MAPK activation, Ca2 mobilization, and cell motility. indirect PMID: 15189145, 11535583 GPR4 appears to couple (at least) with Gi/o to mediate cell proliferation, SRE activation, MAPK activation, Ca2 mobilization, and cell motility. PMID: 15189145, 12220620 GPR12 has been reported to be a moderate-affinity S1P receptor, unresponsive to SPC PMID: 15189145, 12618218 A human orphan receptor GPR63 was reported to act as a low-affinity receptor for S1P, dihydro-S1P, and dioleoylphosphatidic acid. PMID: 15189145, 12618218 A human orphan receptor GPR63 was reported to act as a low-affinity receptor for S1P, dihydro-S1P, and dioleoylphosphatidic acid. PMID: 15189145, 12618218 A human orphan receptor GPR63 was reported to act as a low-affinity receptor for S1P, dihydro-S1P, and dioleoylphosphatidic acid. PMID: 15189145, 12502787 The nuclear hormone receptor peroxisome proliferator-activated receptor (PPARgamma) was proposed as an intracellular receptor for LPA. indirect PMID: 15189145, 11024010, 11160288 In activated T cells, LPA inhibits cell migration but activates IL-2 production/cell proliferation through LPA1. indirect PMID: 15189145, 11024010, 11160288 In activated T cells, LPA inhibits cell migration but activates IL-2 production/cell proliferation through LPA1. PMID: 15189145 FTY720-P can bind to each of four S1P receptors (S1P1, S1P3–S1P5) and activates them with varied potency and efficacy compared to S1P. PMID: 15189145 FTY720-P can bind to each of four S1P receptors (S1P1, S1P3–S1P5) and activates them with varied potency and efficacy compared to S1P. PMID: 15189145 FTY720-P can bind to each of four S1P receptors (S1P1, S1P3–S1P5) and activates them with varied potency and efficacy compared to S1P. PMID: 15189145 FTY720-P can bind to each of four S1P receptors (S1P1, S1P3–S1P5) and activates them with varied potency and efficacy compared to S1P.