Abstract
One of the main research areas in biology from the mid‐1980s through the 1990s was the elucidation of signaling pathways governing cell responses. These studies brought, among other molecules, the small GTPase Rho to the epicenter. Rho signaling research has since expanded to all areas of biology and medicine. Here, we describe how Rho emerged as a key molecule governing cell morphogenesis and movement, how it was linked to actin reorganization, and how the study of Rho signaling has expanded from cultured cells to whole biological systems. We then give an overview of the current research status of Rho signaling in development, brain, cardiovascular system, immunity and cancer, and discuss the future directions of Rho signaling research, with emphasis on one Rho effector, ROCK*. *The Rho GTPase family. Rho family GTPases have now expanded to contain 20 members. Amino acid sequences of 20 Rho GTPases found in human were aligned and the phylogenetic tree was generated by ClustalW2 software (EMBL‐EBI) based on NJ algorithm. The subfamilies of the Rho GTPases are highlighted by the circle and labeled on the right side. Rho cited in this review refers to the original members of Rho subfamily, RhoA, RhoB and RhoC, that are C3 substrates, and, unless specified, not to other members of the Rho subfamily such as Rac, Cdc42, and Rnd.
Highlights
We describe how Rho emerged as a key molecule governing cell morphogenesis and movement, how it was linked to actin reorganization, and how the study of Rho signaling has expanded from cultured cells to whole biological systems
ADP-ribosyltransferase activity, and identified in preparations of botulinum C1 and D toxin an enzyme that ADP-ribosylates a 22 kDa GTP-binding protein in mammalian cells. We reported these findings in the Journal of Biological Chemistry on February 5, 1987
Ridley and Hall addressed these points [14]. They showed that the actin filament structure induced by active RhoA in fibroblasts represents actin stress fibers linked to focal adhesions, that these structures are induced by the addition of serum to the cells, and that this induction was inhibited by microinjection of C3 or ADP-ribosylated Rho, making clear that Rho works as a molecular switch in stimulus-induced stress fiber formation
Summary
One of the main research areas in biology from the mid-1980s through the 1990s was the elucidation of signaling pathways governing cell responses. These studies brought, among other molecules, the small GTPase Rho to the epicenter. Rho signaling research has since expanded to all areas of biology and medicine. We describe how Rho emerged as a key molecule governing cell morphogenesis and movement, how it was linked to actin reorganization, and how the study of Rho signaling has expanded from cultured cells to whole biological systems. With emphasis on one Rho effector, ROCK*
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