Methods of inducing and preventing neurofibromatosis in schwann cells

Abstract

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 - 6 . (canceled) 
     
     
         7 . 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 a blocking agent 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.   
     
     
         8 . (canceled) 
     
     
         9 . A method of inducing neurofibromatosis type 2 (NF2) in Schwann cells, the method comprising:
 Contacting the cells, in vitro, with laminin-1 so as to bind α6β1 integrin sufficiently to activate endogenous kinase Cdc42-Pak, wherein said contacting causes phosphorylation of Schwannomin-S518 in the cells thereby effectively inactivating Schwannomin's tumor suppressor activity.   
     
     
         10 . Cells produced by the method of  claim 9 . 
     
     
         11 . A method of inducing neurofibromatosis type 2 (NF2) in Schwann cells, the method comprising:
 Contacting the cells, in vitro, with NRG-1 so as to bind ErbB2 and/or ErbB3 receptors sufficiently to activate protein kinase A (PKA), wherein said contacting causes phosphorylation of Schwannomin-S518 in the cells thereby effectively inactivating Schwannomin's tumor suppressor activity.   
     
     
         12 . Cells produced by the method of  claim 11 .