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Modification of Ca2+ Regulatory Systems
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
Barbara M. Sanborn, Khursheed Anwer, Yeshao Wen, Enrico Stefani, Ligia Toro, S. P. Singh
There appears to be significant variation in regulation of myometrial PLC between species. In the rat myometrium, has an inhibitory effect,24 while it has a stimulatory effect in nonpregnant guinea pig.19 In the guinea pig, isoproterenol attenuates agonist-stimulated phosphoinositide turnover by a mechanism that does not involve PKA but is pertussis-toxin sensitive.21 Perhaps these differences are due to the relative abundance of different GTP-binding proteins in these preparations. Differential responses associated with altered GTP-binding protein coupling have been noted by others.18,25,26
Regulators of Signal Transduction: Families of GTP-Binding Proteins
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
For the sake of brevity, any discussion of other GTP-binding protein families, namely those involved in the regulation of protein synthesis (e.g., EF-Tu, eIF-2, etc.) and cell motility (e.g., α and β-tubulins), has been omitted. Although all of the GTP-binding proteins mentioned share consensus sequences for GTP-binding proteins, alignment of ras, ARF, or the trimeric G-protein sequences with the tubulins or initiation or elongation factors revealed no significant structural similarities over the length of the protein when compared to a randomly generated group of polypeptides.7a Some excellent reviews have been written on these other families of proteins.8-11
Exchange Factors
Published in Juan Carlos Lacal, Frank McCormick, The ras Superfamily of GTPases, 2017
Another class of GTP-binding proteins that are well-characterized are the elongation and initiation factors involved in protein synthesis. The bacterial protein EF-Tu binds and hydrolyzes GTP. Once it is GDP-bound, it has an absolute requirement for interaction with the exchange factor EF-Ts to allow exchange of GDP for GTP.7 Once again an exchange protein is essential for the function of this GTP-binding protein.
The roles and mechanisms of G3BP1 in tumour promotion
Published in Journal of Drug Targeting, 2019
Cong-Hui Zhang, Jun-Xia Wang, Mei-Lian Cai, Rongguang Shao, Hong Liu, Wu-Li Zhao
Ras is a small GTP-binding protein that is regulated by GTPase activating protein. GAP hydrolyses GTP into GDP and subsequently induces Ras-GTP inactivation [20]. G3BP1 was initially found by coprecipitation with the SH3 domain of Ras-GAP, a negative regulator of Ras [21]. The coprecipitation relied on Ras activation [22]. Furthermore, the interaction between G3BP1 and Ras-GAP is likely to regulate the activity of Ras downstream signalling molecules, such as extracellular regulated protein kinase (ERK) and MEK. Transient knockdown of G3BP1 suppressed the growth of colon cancer HCT116 cells by inhibiting Ras and downstream kinase activity, such as that of ERK and MEK [23]. These findings suggest that G3BP1 promotes tumour cell proliferation by regulating the Ras signalling pathway. Indeed, G3BP1 downregulation blocks Ras signalling. In addition, coprecipitation of G3BP1 and Ras-GAP can be prevented by the polypeptides 38GAP or GAP161, the sequences of which were derived from the G3BP1-interacting sequence of Ras-GAP.
Autocrine and paracrine regulatory functions of platelet serotonin
Published in Platelets, 2018
Elmina Mammadova-Bach, Maximilian Mauler, Attila Braun, Daniel Duerschmied
5-HT can also activate another biological process in platelets, called serotonylation, in particular of small GTPases downstream of the Gq-receptor. Serotonylation requires tissue transglutaminase and factor XIIIa, both activated by intracellular Ca2+ mobilization (15). Transglutaminase mediates the transamidation of small GTPases, like cytoplasmic Ras homolog gene family member A (RhoA) and a small GTP-binding protein Rab4. Serotonylation in turn blocks the inactivation both of molecules. A complex composed of calmodulin and Ca2+ activates guanine exchange factors (GEF), which trigger the exchange of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) on RhoA and Rab4 and induces activation of the respective protein. RhoA and Rab4 are involved in cytoskeleton rearrangement thereby regulating exocytosis of α- and δ-dense granules. It has been shown that 5-HT covalently binds small GTP-binding protein (GTPases, serotonylation), thereby modifying the structure and activity of GTPases, leading to α-granule exocytosis from platelets (15). Consequently, Tph1 knock-out mice (Tph1−/−), which lack the ability to synthesize peripheral 5-HT, but have normal levels of 5-HT in the central nervous system, had decreased α-granule exocytosis (15).
Downregulation of miR-146a promotes tumorigenesis of cervical cancer stem cells via VEGF/CDC42/PAK1 signaling pathway
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Zhihong Dong, Chunxia Yu, Kuerban Rezhiya, Aier Gulijiahan, Xinling Wang
In the present study, the CDC42/PAK1 signaling pathway was activated in TCs’ tumorigenesis and invasion. In addition, CDC42 is an important GTP-binding protein that is associated with various signal transductions [48]. The aberrant expression of CDC42 is involved in tumor genesis and progression, in which p21-activated kinase (PAK) 1 kinase, an effector of the CDC42, can facilitate this process by phosphorylating specific substrates including cyclinD1, cofilin and BAD [49]. Thus, CDC42/PAK1 signaling is an essential modulatory pathway for tumor development [49]. In this study, activated CDC42/PAK1 was associated with down-regulated miR-146a and upregulated VEGF, suggesting miR-146/VEGF/CDC42/PAK1 may play an important role in TCs tumorigenesis and invasion.