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The proto-oncogene ras is an essential gene for the growth and the differentiation for various types of cells. Ras, ras gene product, is a GTP binding protein which controls the signal transduction by GTP hydrolysis. The ras gene is frequently activated by point mutations in various types of human cancers, which results in a decrease in the GTPase activity of its product. A GTPase-activating protein p120 (p120GAP) was identified as a factor which stimulates the GTPase of normal ras gene product p21 but not of the mutated. An NF1 gene was identified as a gene whose loss of function causes an onset of human disorder, neurofibromatosis type I. The NF1 gene encodes a protein which contains a region with a similarity to the catalytic domain of p120GAP. We recently purified a novel Ras GAP whose molecular weight and immunogenecity are different from those of p120GAP and NF1. We named the novel mammalian Ras GAP as Gap1m. Isolation and sequencing of Gap1m cDNA revealed that Gap1m is indeed a novel Ras GAP. We also succeeded in isolation of another novel Ras GAP gene, GapIII/Gap1IP4BP, which is closely related to Gap1m. Recently, it is shown that GapIII/Gap1IP4BP binds inositol-tetrakis phosphate compounds. The overview of these Ras GAP molecules is described.

Heterogeneity of GTPase-activating Proteins for Ras in the Regulation of Ras Signal Transduction Pathway