Fyn is involved in angiotensin II type 2 receptor-induced neurite outgrowth, but not in p42/p44mapk in NG108-15 cells.
In NG108-15 cells, activation of p42/p44(mapk) is essential for induction of neurite outgrowth by angiotensin II (Ang II) type 2 receptor (AT(2)). The aim was to verify whether Fyn, a member of the Src family kinases (SFK), is involved in neurite outgrowth induced by AT(2) activation. Preincubation of cells with PP1, a general inhibitor of the SKF, decreased activation of Rap1 and p42/p44(mapk) and abolished TrkA activation by Ang II or by the AT(2) agonist, CGP42112A. NG108-15 cells were transfected with a Fyn-WT and a Fyn-DN expressing vector. Fyn-WT was sufficient to induce neurite outgrowth, although transfection with Fyn-DN abolished neurite elongation. However, the Fyn-DN form failed to affect activation of TrkA, Rap1 or p42/p44(mapk) by Ang II. Thus, although SKF activity is required to achieve AT(2)-induced activation of TrkA, Rap1 and p42/p44(mapk), Fyn is essential for AT(2) receptor-induced neurite outgrowth, but not in AT(2) signaling leading to p42/p44(mapk) activation.
Guimond
M-O
MO
Service d'Endocrinologie, Département de Médecine Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, Québec, Canada. swanwickc@mail.nih.gov
Roberge
Claude
C
Gallo-Payet
N
N
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D020917:Receptor, trkA; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020827:rap1 GTP-Binding Proteins