Small molecular weight GTP-binding proteins and signal transduction.
We have separated multiple GTP-binding proteins (G proteins) having Mr values of about 20,000 (small Mr G proteins) from bovine brain membranes, purified to near homogeneity and characterized two novel G proteins designated as smg p25A and smg p21, the c-Ki-ras protein (c-Ki-ras p21) and the two rho proteins (rho p20 and rho p21). smg p25A is present abundantly in brain and adrenal medulla. This G protein is also found in rat pheochromocytoma PC-12 cells, and its mRNA level increased 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 neuronal 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 the actions similar and/or antagonistic to those of ras p21s. In fact, smg p21 has been found to be identical with the protein encoded by the Krev-1 gene recently isolated as a gene suppressing the transforming action of Ki-ras p21 in NIH/3T3 cells. On the other hand, rho p20 and rho p21 are ADP-ribosylated by an ADP-ribosyltransferase contained or contaminated in botulinum toxin type C1, presumably C3. Botulinum ADP-ribosyltransferase C3 has recently been shown to induce morphological changes similar to those induced by ras p21 in fibroblasts. Thus, 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.
Yamamoto
K
K
Department of Biochemistry, Kobe University School of Medicine, Japan.
Tanimoto
T
T
Kim
S
S
Kikuchi
A
A
Takai
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D002417:Cattle; D019204:GTP-Binding Proteins / Q000302:isolation & purification* / Q000378:metabolism / Q000502:physiology; D015689:Oncogene Protein p21(ras) / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*
D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras)