GTP-binding Proteins as Cellular Signal Transducer

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This research project, entitled "GTP-binding Proteins as Cellular Signal Transducer" and supported by Grant-in-Aid for Scientific Research on Priority Areas, consisted of two groups with the following research subjects, i, e., the first group with "Mechanisms and Roles of alphabetagamma-Hetero-trimeric G-Proteins" ant the second group with "Mechanisms and Roles of Low-molecular GTP-binding proteins". Although both of these big families of GTP-binding proteins play essential roles in membrane receptor-initiated intracellular signaling network, their functions as signaling proteins are distinctly different from each other. The former is coupled to, and mediated all the intracellular signals triggered by, receptors whose common protein structure is characterized by particular seven membrane-spanning helical domains and whose physiological agonists include essentially all of neurotransmitters, neuropeptides and protein hormones (except insulin). The latter plays a pivotal role in intracell … More ular signaling cascades arising from stimulation of receptors for growth factors (including insulin), cytokines and other autacoids. These receptors are distinctly different from heterotrimeric G-protein-coupled receptors in structure and function ; the receptor proteins possess tyrosine kinase domains or, alternatively, though having no endogenous kinase activity, activate non-receptor-type protein tyrosine kinases at the first step of triggered intracellular signaling. The low-molecular GTP-binding proteins, such as Ras, Rho.Rab and other subfamilies, function to link these signaling eventually to cell proliferation, gene expression, morphological changes, cell-cell contact and intracellular protein traffics. All the investigators belonging to either of these two groups of the project have made their own original contributions in these internationally very competitive fields of research. Particularly striking contributions were those made by the head investigator of the project and his colleagues. They have proposed new mechanisms, related to PtdIns 3-kinase, of the "crosstalk" between these two different signaling systems. Less