Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1. Sphk1 null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in most Sphk1-/- tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from the Sphk1 -/- mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs of Sphk1 -/- mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in the Sphk1 null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with these Sphk1 null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.
机构:
Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R ChinaShanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R China
Zhao, Zhen
Wang, Ruixue
论文数: 0引用数: 0
h-index: 0
机构:
Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R ChinaShanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R China
Wang, Ruixue
Huo, Zhijun
论文数: 0引用数: 0
h-index: 0
机构:
Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R ChinaShanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R China
Huo, Zhijun
Li, Chunlei
论文数: 0引用数: 0
h-index: 0
机构:
Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R ChinaShanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R China
Li, Chunlei
Wang, Zhiyong
论文数: 0引用数: 0
h-index: 0
机构:
Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R ChinaShanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, 1111 Zhongshanbeiyi Rd, Shanghai 200437, Peoples R China
机构:
Mitsubishi Tanabe Pharma Corp, Div Res, Med Chem Res Labs 1, Aoba Ku, Yokohama, Kanagawa 2270033, JapanMitsubishi Tanabe Pharma Corp, Div Res, Med Chem Res Labs 1, Aoba Ku, Yokohama, Kanagawa 2270033, Japan
机构:
Hokkaido Univ, Biochem Lab, Fac Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan
Hokkaido Univ, Lab Biomembrane & Biofunct Chem, Fac Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, JapanHokkaido Univ, Lab Biomembrane & Biofunct Chem, Facil Adv Life Sci, Kita Ku, Sapporo, Hokkaido 0010021, Japan
Kihara, Akio
Igarashi, Yasuyuki
论文数: 0引用数: 0
h-index: 0
机构:
Hokkaido Univ, Lab Biomembrane & Biofunct Chem, Facil Adv Life Sci, Kita Ku, Sapporo, Hokkaido 0010021, Japan
Hokkaido Univ, Lab Biomembrane & Biofunct Chem, Fac Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, JapanHokkaido Univ, Lab Biomembrane & Biofunct Chem, Facil Adv Life Sci, Kita Ku, Sapporo, Hokkaido 0010021, Japan
Igarashi, Yasuyuki
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS,
2008,
1781
(09):
: 496
-
502