Neuregulin-induced association of SOS Ras exchange protein with HER2(erhB2)/HER3(erbB3) receptor complexes in Schwann cells through a specific Grb2-HER2(erb62) interaction

Neuregulins are members of the epidermal growth factor family of related li gands that exert pleotropic effects during development on the Schwann cell lineage. The receptor complex activated by neuregulin in Schwann cells cons ists of HER2 (erbB2) and HER3 (erbB3). The intracellular signaling events t hat follow activation of the HER2/HER3 receptor complex in primary cells, a nd in particular in Schwann cells, are poorly understood. We have found tha t neuregulin induces the rapid association of the guanine nucleotide exchan ge factor SOS with the HER2/HER3 receptor complex. The association of SOS w ith the HER2/HER3 receptor complex is preceded by the rapid association of Grb2 with the HER2/HER3 receptor complex. Far Western analysis indicates th at Grb2 and SOS bind exclusively to HER2 in the HER2/HER3 receptor complex. Copyright (C) 2001 S. Karger AG, Basel.