[ras p21-like small MW GTP-binding proteins in transmembrane signaling]

Abstract

We have separated multiple GTP-binding proteins (G proteins) having Mr values of about 20,000 (small MW G proteins) from bovine brain membranes, purified to near homogeneity and characterized two novel G proteins designated as smg p25A and smg p21, c-Ki-ras p21 and rho p20. smg p25A is specifically found in neural tissue and adrenal medulla. This G protein is also found in rat pheochromocytoma PC-12 cells, and its mRNA level increases after differentiation of the cells into neuron-like cells in response to nerve growth factor or dibutyryl cyclic AMP. These results suggest that smg p25A plays an important role in the regulation of neural functions. In contrast, smg p21 is found in most tissues. This G protein has the same putative effector domain as ras p21s, suggesting that smg p21 exerts actions similar and/or antagonistic to those of ras p21s. In fact, smg p21 has been found to be identical with the ras-suppressor gene, designated as Krev-1, recently isolated by Noda's group. On the other hand, rho p20 is ADP-ribosylated by botulinum toxin. This toxin, known to be a neurotoxin, has recently been shown to induce the morphological changes similar to those induced by ras p21 in fibroblasts. Thus, ras p21-like small Mr G proteins are part of a huge network of intracellular regulatory systems and play important roles in the regulation of various cell functions including cell transformation, proliferation and differentiation.