Methods of inducing and preventing neurofibromatosis in Schwann cells
The invention provides a method of inducing neurofibromatosis type 2 (NF2) in Schwann cells. The method comprises contacting the cells with laminin-1 so as to bind α6β1 integrin sufficiently to activate endogenous kinase Cdc42-Pak; and phosphorylating Schwannomin-S518 in the cells by the activated kinase, effectively inactivating Schwannomin's tumor suppressor activity and allowing proliferation of subconfluent Schwann cells, thereby modeling NF2. The invention also includes a method of preventing a Schwann cell from forming a tumor by contacting the cell with an amount of tyrphostin AG825 sufficient to inhibit a receptor selected from ErB2, ErB3, β1 integrins and combinations thereof, so as to prevent phosphorylation of Schwannomin-S815 by one or more endogenous kinases.
1. A method of circumventing a lack of neurofibromatosis type 2 tumor suppressor activity in Schwann cells, the method comprising:
contacting Schwann cells lacking neurofibromatosis type 2 suppressor activity with an effective amount of tyrphostin AG825 that inhibits normal function of a receptor selected from the group consisting of ErbB2, ErbB3, β1 integrins and combinations thereof;
wherein the contacting prevents the cells from receiving a growth signal normally inhibited by a neurofibromatosis type 2 tumor suppressor, and
wherein the Schwann cells comprise a mutated Schwannomin protein that causes the Schwann cells to lack neurofibromatosis type 2 suppressor activity.
2. A method of preventing a Schwann cell from forming a tumor associated with neurofibromatosis type 2, the method comprising:
contacting a Schwann cell lacking neurofibromatosis type 2 suppressor activity with an amount of tyrphostin AG825 sufficient to inhibit a receptor selected from the group consisting of ErbB2, ErbB3, β1 integrins and combinations thereof, wherein the contacting prevents the cell from receiving a growth signal normally inhibited by a neurofibromatosis type 2 tumor suppressor, and
wherein the Schwann cells comprise a mutated Schwannomin protein that causes the Schwann cells to lack neurofibromatosis type 2 suppressor activity.