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/p44mapk is essential for induction of neurite outgrowth by angiotensin II (Ang II) type 2 receptor (AT2). The aim was to verify whether Fyn, a member of the Src family kinases (SFK), is involved in neurite outgrowth induced by AT2 activation. Preincubation of cells with PP1, a general inhibitor of the SKF, decreased activation of Rap1 and p42/p44mapk and abolished TrkA activation by Ang II or by the AT2 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/p44mapk by Ang II. Thus, although SKF activity is required to achieve AT2-induced activation of TrkA, Rap1 and p42/p44mapk, Fyn is essential for AT2 receptor-induced neurite outgrowth, but not in AT2 signaling leading to p42/p44mapk activation.