Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis

doi:10.1016/0092-8674(92)90407-4

Cell

Volume 69, Issue 2, 17 April 1992, Pages 265-273

https://doi.org/10.1016/0092-8674(92)90407-4 Get rights and content

Abstract

Tumor cell lines derived from malignant schwannomas removed from patients with neurofibromatosis type 1 (NF1) have been examined for the level of expression of NF1 protein. All three NF1 lines examined expressed lower levels of NF1 protein than control cells, and the level in one line was barely detectable. The tumor lines expressed normal levels of p120^GAP and p21^ras. Although the p21^ras proteins isolated from the tumor cells had normal (nonmutant) biochemical properties in vitro, they displayed elevated levels of bound GTP in vivo. The level of total cellular GAP-like activity was reduced in extracts from the tumor line that expresses very little NF1 protein. Introduction of the catalytic region of GAP into this line resulted in morphological reversion and lower in vivo GTP binding by endogenous p21^ras. These data implicate NF1 protein as a tumor suppressor gene product that negatively regulates p21^ras and define a “positive” growth role for ras activity in NF1 malignancies.

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Cell

ArticleAbnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis

Abstract

Cell

Cell

Cell

Cell

J. Biol. Chem.

J. Biol. Chem.

Cell

Trends Genet.

Genomics

Trends Genet.

Cell

Cell

Cell

Trends Biochem. Sci.

Cell

Cell

Guanosine triphosphatase activating protein (GAP) interacts with the p21 ras effector binding domain

Science

ras genes

Annu. Rev. Biochem.

Differential regulation of ras GAP and neurofibromatosis gene product activities

Nature

The GTPase superfamily: a conserved switch for diverse cell functions

Nature

The GTPase superfamily: conserved structure and molecular mechanism

Nature

The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product

Nature

The product of the neurofibromatosis type 1 gene is expressed at highest abundance in neurons, Schwann cells, and oligodendrocytes

Neuron

Identification and characterization of the neurofibromatosis type 1 protein product

A ras effector domain mutant which is temperature sensitive for cellular transformation: interactions with GTPase-activating protein and NF-1

Mol. Cell. Biol.

Inhibition of cell growth by lovastatin is independent of ras function

Cancer Res.

Suppression of src transformation by overexpression of full-length GTPase activating protein (GAP) or of the GAP C terminus

Mol. Cell. Biol.

Altered guanine nucleotide binding and H-ras transforming and differentiating activities

Oncogene

Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases

Nature

Article
Abnormal regulation of mammalian p21^ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis