Regulatory role of sphingosine kinase and sphingosine-1-phosphate receptor signaling in progenitor/stem cells

Figure 1 Diversion of myogenic stimulation at the S1P2 receptor level (hypothetical scheme). Activation of S1P2 receptor signaling results in dual effects in muscle progenitor cells: Erk1/2 mediates inhibition of serum-induced proliferation, while p38MAPK[78,79], phosphatidylinositol 3-kinase (PI3K)[72] and activator of transcription 3 (STAT3)-dependent pathways[82] are required for S1P-trigerred activation of myogenic differentiation. The role of RhoA signaling is unclear. Question marks indicate unclear signaling regulation. S1P: Sphingosine-1-phosphate.

Figure 2 Sphingosine kinase/sphingosine-1-phosphate signaling axis in neural stem/progenitor cells (hypothetical scheme). Activation of S1P3 receptor signaling and activation of neural cell progenitor differentiation are mediated by various downstream effectors including PKC, PI3K/Akt, MAPK/Erk1/2, NT3, and CREB/NF-κB TFs. SphK: Sphingosine kinase; S1P: Sphingosine-1-phosphate; CREB: cAMP-response element binding protein; NT3: Neurotrophin 3; TF: Transcription factor.

Figure 3 Differentiating effects of sphingosine kinase/sphingosine-1-phosphate inhibition and S1P receptor activation on downstream signaling pathways in various stem/progenitor cells. SphK: Sphingosine kinase; S1P: Sphingosine-1-phosphate; CREB: cAMP-response element binding protein; YAP: YES-associated protein.