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. 2014 Dec 19;15(12):23725–23748. doi: 10.3390/ijms151223725

Figure 3.

Figure 3

The biphasic responses of aminoacyl-tRNA synthetase interacting multifunctional protein 1 (AIMP1) and endothelial monocyte activating polypeptide II (EMAP II) on angiogenesis. (1) Caspase 7 cleaves the C-terminal EMAP II peptide from AIMP1, releasing EMAP II from the multi-synthetase complex; (2) Alternatively, AIMP1 is released by unknown processes; (3) Both EMAP II and AIMP1 are secreted from the cell by mechanisms that remain to be determined; (4) At low concentrations (perhaps corresponding to early portions of the AIMP1/EMAP II signaling responses in vivo) EMAPII and AIMP1 bind to surface receptors, activating various kinase cascades; (5) These kinase cascades induce the expression of tumor necrosis factor α (TNFα); (6) TNFα is secreted from the cell and mediates angiogenesis through canonical TNFα pathways; (7) At high concentrations (perhaps corresponding to prolonged exposure in vivo), AIMP1 and EMAP II induce the expression of the TNFα-receptor (TNFR); and (8) Over-stimulation of TNFR by TNFα induces apoptosis through signaling by the TNFR death-domain, resulting in an anti-angiogenic response.