Integrin 91 is a receptor for nerve growth factor and other neurotrophins

The integrin 91 is a multifunctional receptor that interacts with a variety of ligands including vascular cell adhesion molecule 1, tenascin C and osteopontin. We found that this integrin is a receptor for nerve growth factor (NGF) and two other neurotrophins, brain-derived neurotrophic factor and NT3, using a cell adhesion assay with the 9SW480 cell line. Interaction of 91 with NGF was confirmed in an ELISA assay by direct binding to purified integrin. 91 integrin binds to neurotrophins in a manner similar to another common neurotrophin receptor, p75^NTR (NGFR), although 91 activity is correlated with induction of pro-survival and pro-proliferative signaling cascades. This property of 91 resembles the interaction of NGF with a high affinity receptor, TrkA, however, this integrin shows a low affinity for NGF. NGF induces chemotaxis of cells expressing 91 and their proliferation. Moreover, 91 integrin is a signaling receptor for NGF, which activates the MAPK (Erk1/2) pathway. The 91-dependent chemotactic ability of NGF appears to result from the activation of paxillin.