02020nam a2200289Ia 4500 MX-MdCICY 20260521091008.0 CICY B-6367 Substance P-induced activation of p42/44 mitogen-activated protein kinase associated with cell proliferation in human tracheal smooth muscle cells Cellular Signalling, 14(11), p.913-923, 2002 Substance P (SP)released from sensory nerve endings in the airways induces several responses including cell proliferation. However, the mechanisms were not completely understood in tracheal smooth muscle cells (TSMCs). We therefore investigated the effect of SP on cell proliferation and activation of p42/p44 mitogen-activated protein kinase (MAPK)in these cells. SP stimulated [3H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and concentration-dependent manner in TSMCs. Both DNA synthesis and phosphorylation of MAPK in response to SP were attenuated by pretreatment with pertussis toxin, genistein, D609, U73122, staurosporine, removal of Ca2+ by BAPTA/AM plus EGTA, PD98059, and SB202190. Furthermore, overexpression of dominant negative mutants, H-Ras-15A and Raf-N4, significantly suppressed p42/p44 MAPK activation induced by SP and PDGF-BB. These results conclude that the mitogenic effect of SP was mediated through the activation of Ras/Raf/MEK/MAPK pathway, which was modulated by PC-PLC, PI-PLC, Ca2+, and PKC in cultured human TSMCs. CELL PROLIFERATION MAPK PROTEIN KINASE C SUBSTANCE P TYROSINE KINASE Yang, C-M. Hsiao, L.-D. Chien, C-S. Lin, C-C. Luo, S-F. Wang, C-C. https://drive.google.com/file/d/105JNXk3lOpzeL-OPfHSaKz5owQs5v_gJ/view?usp=drivesdk Para ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx Loc REF1 250602s9999 xx |||||s2 |||| ||und|d 16650 16650 0 0 Loc 0 0 F1 CICY CICY RE 2025-06-25 0 B-6367 2025-06-25 12:46:41 2025-06-25 REF1