Neuregulin induces the rapid association of focal adhesion kinase with theerbB2-erbB3 receptor complex in Schwann cells

Neuregulins signal cells by binding to an activating hetero- and homodimeri c forms of the neuregulin receptors HER2 (erbB2), HER3 (erbB3), and HER4 (e rbB4). Axonally derived neuregulin signals myelin forming cells of the cent ral and peripheral nervous systems through different receptor complexes: ol igodendrocytes through erbB2/erbB4 heterodimers and Schwann cells through e rbB2/erbB3 heterodimers. Since the leading edge of myelinating cells intera cts directly with the axonal surface, we were interested in determining if signaling molecules localized at the leading edge associate with activated neuregulin receptors. We found a novel association between neuregulin recep tors and focal adhesion kinase (FAK) in primary cultures of Schwann cells. Following stimulation with ligand, maximal binding of FAK to HER2 occurred by 1 min whereas maximal binding to HER3 was delayed to similar to 7 min. F AK is localized in focal adhesions of Schwann cells. We have previously sho wn HER2 and HER3 are distributed evenly throughout the plasmalemma. Neuregu lins thus use FAK to transmit intracellular signals and the differential ki netics of FAK association with individual neuregulin receptors, as well as its restricted subcellular localization, may play a role in specifying biol ogic responses. (C) 2000 Academic Press.