title: Integrin alpha9 beta1 is a receptor for nerve growth factor and other neurotrophins.
abstract: The integrin alpha9beta1 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 alpha9SW480 cell line. Interaction of alpha9beta1 with NGF was confirmed in an ELISA assay by direct binding to purified integrin. alpha9beta1 integrin binds to neurotrophins in a manner similar to another common neurotrophin receptor, p75(NTR) (NGFR), although alpha9beta1 activity is correlated with induction of pro-survival and pro-proliferative signaling cascades. This property of alpha9beta1 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 alpha9beta1 and their proliferation. Moreover, alpha9beta1 integrin is a signaling receptor for NGF, which activates the MAPK (Erk1/2) pathway. The alpha9beta1-dependent chemotactic ability of NGF appears to result from the activation of paxillin.
authors.affiliation: Department of Neuroscience, Center for Neurovirology and Cancer Biology, Temple University, School of Medicine, Philadelphia, PA 19122, USA.
authors.forename: Izabela
authors.initials: I
authors.lastname: Staniszewska
authors.forename: Ilker K
authors.initials: IK
authors.lastname: Sariyer
authors.forename: Shimon
authors.initials: S
authors.lastname: Lecht
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Brown
authors.forename: Erin M
authors.initials: EM
authors.lastname: Walsh
authors.forename: George P
authors.initials: GP
authors.lastname: Tuszynski
authors.forename: Mahmut
authors.initials: M
authors.lastname: Safak
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarovici
authors.forename: Cezary
authors.initials: C
authors.lastname: Marcinkiewicz
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016023:Integrins; D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; C113256:integrin alpha 9 beta 1; D020932:Nerve Growth Factor; D020917:Receptor, trkA