scholarly journals Emerging Roles of Ephexins in Physiology and Disease

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 87
Author(s):  
Kwanhyeong Kim ◽  
Sang-Ah Lee ◽  
Daeho Park
Keyword(s):  
Neural Development ◽  
Rho Gtpases ◽  
B Cell Lymphoma ◽  
Guanine Nucleotide Exchange Factors ◽  
Regulatory Mechanisms ◽  
Eph Receptors ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors ◽  
Cellular Events

Dbl (B-cell lymphoma)-related guanine nucleotide exchange factors (GEFs), the largest family of GEFs, are directly responsible for the activation of Rho family GTPases and essential for a number of cellular events such as proliferation, differentiation and movement. The members of the Ephexin (Eph-interacting exchange protein) family, a subgroup of Dbl GEFs, initially were named for their interaction with Eph receptors and sequence homology with Ephexin1. Although the first Ephexin was identified about two decades ago, their functions in physiological and pathological contexts and regulatory mechanisms remained elusive until recently. Ephexins are now considered as GEFs that can activate Rho GTPases such as RhoA, Rac, Cdc42, and RhoG. Moreover, Ephexins have been shown to have pivotal roles in neural development, tumorigenesis, and efferocytosis. In this review, we discuss the known and proposed functions of Ephexins in physiological and pathological contexts, as well as their regulatory mechanisms.

scholarly journals Hormones Secretion and Rho GTPases in Neuroendocrine Tumors

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1859
Author(s):  
Laura Streit ◽  
Laurent Brunaud ◽  
Nicolas Vitale ◽  
Stéphane Ory ◽  
Stéphane Gasman
Keyword(s):  
Neuroendocrine Tumors ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Secretory Activity ◽  
Guanine Nucleotide Exchange Factors ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors ◽  
Gtpase Activating Proteins

Neuroendocrine tumors (NETs) belong to a heterogeneous group of neoplasms arising from hormone secreting cells. These tumors are often associated with a dysfunction of their secretory activity. Neuroendocrine secretion occurs through calcium-regulated exocytosis, a process that is tightly controlled by Rho GTPases family members. In this review, we compiled the numerous mutations and modification of expression levels of Rho GTPases or their regulators (Rho guanine nucleotide-exchange factors and Rho GTPase-activating proteins) that have been identified in NETs. We discussed how they might regulate neuroendocrine secretion.

scholarly journals Requirements for Vav Guanine Nucleotide Exchange Factors and Rho GTPases in FcγR- and Complement-Mediated Phagocytosis

Immunity ◽  
2006 ◽  
Vol 24 (3) ◽  
pp. 305-316 ◽  
Author(s):  
Amy B. Hall ◽  
M. Angelica Martinez Gakidis ◽  
Michael Glogauer ◽  
Julie L. Wilsbacher ◽  
Sizhen Gao ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Guanine Nucleotide Exchange Factors ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors

scholarly journals Computational Prediction of Hot Spots and Binding Site of Inhibitor NSC23766 on Rac1 Binding With Tiam1

2021 ◽  
Vol 8 ◽  
Author(s):  
Chunwen Zheng ◽  
Xiaodong Wu ◽  
Ruijie Zeng ◽  
Lirui Lin ◽  
Liyan Xu ◽  
...  
Keyword(s):  
Hot Spots ◽  
Binding Free Energy ◽  
Computational Prediction ◽  
Guanine Nucleotide Exchange Factors ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors ◽  
Cellular Events ◽  
T Lymphoma ◽  
Multiple Signaling

Rac1 is a small signaling protein, which belongs to the Rho subfamily of Ras superfamily. It is activated by binding GTP and inactivated by exchanging GDP for GTP. The ability of nucleotide exchange depends on guanine nucleotide exchange factors (GEFs) family proteins. T-lymphoma invasion and metastasis factor 1 (Tiam1) is a member of GEFs. Rac1 participates in multiple signaling pathways and regulates various cellular events by interacting with GEFs. Particularly, it is involved in the development and progression of various kinds of tumors. In this paper, we have studied the detailed interaction between Rac1 and Tiam1. Seven residues on Rac1 are predicted to be important for the interaction with Tiam1, i.e. E31, Y32, D38, N39, Y64, D65 and W56. All these residues are located on the switch 1 and 2 domains which are the interface between Rac1 and Tiam1, except W56. In addition, we analyzed how inhibitor NSC23766 interacts with Rac1. Our docking results show that NSC23766 binds to the same region as Tiam1. Several residues, i.e. F37, D38, N39, W56, Y64, L67, L70 and S71, contribute much to binding free energy. These findings are very useful for the structure-based design of inhibitors toward Rac1.

The Trio family of guanine-nucleotide-exchange factors: regulators of axon guidance

2001 ◽  
Vol 114 (11) ◽  
pp. 1973-1980 ◽  
Author(s):  
Jack Bateman ◽  
David Van Vactor
Keyword(s):  
Axon Guidance ◽  
Neural Development ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Guanine Nucleotide Exchange Factors ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factors

Axon guidance requires the integration of diverse guidance signals presented by numerous extracellular cues and cell-cell interactions. The molecular mechanisms that interpret these signals involve networks of intracellular signaling proteins that coordinate a variety of responses to the environment, including remodeling and assembly of the actin cytoskeleton. Although it has been clear for some time that Rho family GTPases play a central role in the orchestration of cytoskeletal assembly, our understanding of the components that regulate these important molecules is far more primitive. Recent functional studies of the Trio family of guanine-nucleotide-exchange factors reveal that Trio proteins play a vital role in neuronal cell migration and axon guidance. Although the molecular analysis of Trio proteins is still in its infancy, accumulated evidence suggests that Trio proteins function as integrators of multiple upstream inputs and as activators of multiple downstream pathways. Future studies of these mechanisms promise to yield insights not only into neural development but also into the ongoing function and remodeling of the adult nervous system.

Sign in / Sign up

Export Citation Format

Share Document