Structure and function of RLIP76 (RalBP1): an intersection point between Ras and Rho signalling

2014 ◽  
Vol 42 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Helen R. Mott ◽  
Darerca Owen
Keyword(s):  
G Proteins ◽  
Coiled Coil ◽  
Intersection Point ◽  
Small Gtpases ◽  
Protein Domain ◽  
Atp Binding ◽  
Interacting Protein ◽  
Switch Regions ◽  
Ras Family ◽  
Rho Family

RLIP76 (Ral-interacting protein of 76 kDa) [also known as RalBP1 (Ral-binding protein 1)] is an effector for the Ral family small GTPases. RLIP76 has been implicated in a number of cell processes, including receptor-mediated endocytosis, cell migration, mitochondrial division and metabolite transport. RLIP76 has two recognizable domains in the centre of the protein sequence: a GAP (GTPase-activating protein) domain for the Rho family G-proteins and an RBD (Ral-binding domain). The remainder of RLIP76 has no discernable homology with other proteins. The RBD forms a simple coiled-coil of two α-helices, which interacts with RalB by binding to both of the nucleotide-sensitive ‘switch’ regions. Both of these RLIP76 helices are involved in the interaction with Ral, but the interhelix loop is left free. This is the location of one of the two ATP-binding sites that have been identified in RLIP76 and suggests that Ral interaction would not prevent ATP binding. The structure of the RhoGAP–RBD dyad shows that the two domains are fixed in their orientation by a relatively rigid linker. This domain arrangement allows the two domains to engage Rho family and Ral small G-proteins simultaneously at the membrane. This suggests that RLIP76 is a node for Rho and Ras family signalling.

scholarly journals Grit, a GTPase-Activating Protein for the Rho Family, Regulates Neurite Extension through Association with the TrkA Receptor and N-Shc and CrkL/Crk Adapter Molecules

2002 ◽  
Vol 22 (24) ◽  
pp. 8721-8734 ◽  
Author(s):  
Takeshi Nakamura ◽  
Misako Komiya ◽  
Kiyoaki Sone ◽  
Eiji Hirose ◽  
Noriko Gotoh ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Neuronal Cells ◽  
Small Gtpases ◽  
Actin Dynamics ◽  
Gtpase Activating Protein ◽  
Interacting Protein ◽  
High Affinity Receptor ◽  
Rho Family

ABSTRACT Neurotrophins are key regulators of the fate and shape of neuronal cells and act as guidance cues for growth cones by remodeling the actin cytoskeleton. Actin dynamics is controlled by Rho GTPases. We identified a novel Rho GTPase-activating protein (Grit) for Rho/Rac/Cdc42 small GTPases. Grit was abundant in neuronal cells and directly interacted with TrkA, a high-affinity receptor for nerve growth factor (NGF). Another pool of Grit was recruited to the activated receptor tyrosine kinase through its binding to N-Shc and CrkL/Crk, adapter molecules downstream of activated receptor tyrosine kinases. Overexpression of the TrkA-binding region of Grit inhibited NGF-induced neurite elongation. Further, we found some tendency for neurite promotion in full-length Grit-overexpressing PC12 cells upon NGF stimulation. These results suggest that Grit, a novel TrkA-interacting protein, regulates neurite outgrowth by modulating the Rho family of small GTPases.

scholarly journals Identification of Tetratricopeptide Repeat 1 as an Adaptor Protein That Interacts with Heterotrimeric G Proteins and the Small GTPase Ras

2003 ◽  
Vol 23 (11) ◽  
pp. 3847-3858 ◽  
Author(s):  
Caroline Marty ◽  
Darren D. Browning ◽  
Richard D. Ye
Keyword(s):  
G Proteins ◽  
Mammalian Cells ◽  
Active Form ◽  
Adaptor Protein ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Tetratricopeptide Repeat ◽  
Heterotrimeric G Proteins ◽  
Interacting Protein

ABSTRACT The biological functions of heterotrimeric G proteins and small GTPases are modulated by both extracellular stimuli and intracellular regulatory proteins. Using Saccharomyces cerevisiae two-hybrid screening, we identified tetratricopeptide repeat 1 (TPR1), a 292-amino-acid protein with three TPR motifs, as a Gα16-binding protein. The interaction was confirmed both in vitro and in transfected mammalian cells, where TPR1 also binds to several other Gα proteins. TPR1 was found to interact with Ha-Ras preferentially in its active form. Overexpression of TPR1 promotes accumulation of active Ras. TPR1 was found to compete with the Ras-binding domain (RBD) of Raf-1 for binding to the active Ras, suggesting that it may also compete with Ras GTPase-activating protein, thus contributing to the accumulation of GTP-bound Ras. Expression of Gα16 strongly enhances the interaction between TPR1 and Ras. Removal of the TPR1 N-terminal 112 residues abolishes potentiation by Gα16 while maintaining the interaction with Gα16 and the ability to discriminate active Ras from wild-type Ras. We have also observed that LGN, a Gαi-interacting protein with seven TPR motifs, binds Ha-Ras. Thus, TPR1 is a novel adaptor protein for Ras and selected Gα proteins that may be involved in protein-protein interaction relating to G-protein signaling.

scholarly journals Chemotactic Signaling Pathways in Neutrophils: from Receptor to Actin Assembly

2002 ◽  
Vol 13 (3) ◽  
pp. 220-228 ◽  
Author(s):  
Gregor Cicchetti ◽  
Philip G. Allen ◽  
Michael Glogauer
Keyword(s):  
G Proteins ◽  
Neutrophil Function ◽  
Small Gtpases ◽  
Regulatory Proteins ◽  
Heterotrimeric G Proteins ◽  
Actin Assembly ◽  
Receptor Ligand ◽  
Downstream Effectors ◽  
Ligand Interactions ◽  
Rho Family

In this review, we present an overview of the signaling elements between neutrophil chemotactic receptors and the actin cytoskeleton that drives cell motility. From receptor-ligand interactions, activation of heterotrimeric G-proteins, their downstream effectors PLC and PI-3 kinase, the activation of small GTPases of the Rho family, and their regulation of particular cytoskeletal regulatory proteins, we describe pathways specific to the chemotaxing neutrophil and elements documented to be important for neutrophil function.

Functions of Rho family of small GTPases and Rho-associated coiled-coil kinases in bone cells during differentiation and mineralization

2017 ◽  
Vol 1861 (5) ◽  
pp. 1009-1023 ◽  
Author(s):  
Agnieszka Strzelecka-Kiliszek ◽  
Saida Mebarek ◽  
Monika Roszkowska ◽  
René Buchet ◽  
David Magne ◽  
...  
Keyword(s):  
Bone Cells ◽  
Coiled Coil ◽  
Small Gtpases ◽  
Rho Family

scholarly journals Crystal structure of the Rab-binding domain of Rab11 family-interacting protein 2

2020 ◽  
Vol 76 (8) ◽  
pp. 357-363
Author(s):  
Aoife Mairead Kearney ◽  
Amir Rafiq Khan
Keyword(s):  
Crystal Structure ◽  
Membrane Trafficking ◽  
Coiled Coil ◽  
Small Gtpases ◽  
Binding Domain ◽  
Effector Proteins ◽  
Interacting Protein ◽  
Arginine Residues ◽  
Polar Interactions ◽  
Endocytic Compartments

The small GTPases Rab11, Rab14 and Rab25 regulate membrane trafficking through the recruitment of Rab11 family-interacting proteins (FIPs) to endocytic compartments. FIPs are multi-domain effector proteins that have a highly conserved Rab-binding domain (RBD) at their C-termini. Several structures of complexes of Rab11 with RBDs have previously been determined, including those of Rab11–FIP2 and Rab11–FIP3. In addition, the structures of the Rab14–FIP1 and Rab25–FIP2 complexes have been determined. All of the RBD structures contain a central parallel coiled coil in the RBD that binds to the switch 1 and switch 2 regions of the Rab. Here, the crystal structure of the uncomplexed RBD of FIP2 is presented at 2.3 Å resolution. The structure reveals antiparallel α-helices that associate through polar interactions. These include a remarkable stack of arginine residues within a four-helix bundle in the crystal lattice.

scholarly journals Function of small GTPases in Dictyostelium macropinocytosis

2018 ◽  
Vol 374 (1765) ◽  
pp. 20180150 ◽  
Author(s):  
Thomas D. Williams ◽  
Peggy I. Paschke ◽  
Robert R. Kay
Keyword(s):  
G Proteins ◽  
Large Scale ◽  
Small Gtpases ◽  
Ras Proteins ◽  
Cell Interior ◽  
Ras Activation ◽  
Specific Uptake ◽  
Rho Family ◽  
The Individual ◽  
Small G Proteins

Macropinocytosis—the large-scale, non-specific uptake of fluid by cells—is used by Dictyostelium discoideum amoebae to obtain nutrients. These cells form circular ruffles around regions of membrane defined by a patch of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the activated forms of the small G-proteins Ras and Rac. When this ruffle closes, a vesicle of the medium is delivered to the cell interior for further processing. It is accepted that PIP3 is required for efficient macropinocytosis. Here, we assess the roles of Ras and Rac in Dictyostelium macropinocytosis. Gain-of-function experiments show that macropinocytosis is stimulated by persistent Ras activation and genetic analysis suggests that RasG and RasS are the key Ras proteins involved. Among the activating guanine exchange factors (GEFs), GefF is implicated in macropinocytosis by an insertional mutant. The individual roles of Rho family proteins are little understood but activation of at least some may be independent of PIP3. This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.

scholarly journals Regulated CD44 Cleavage under the Control of Protein Kinase C, Calcium Influx, and the Rho Family of Small G Proteins

1999 ◽  
Vol 274 (36) ◽  
pp. 25525-25534 ◽  
Author(s):  
Isamu Okamoto ◽  
Yoshiaki Kawano ◽  
Mitsuhiro Matsumoto ◽  
Moritaka Suga ◽  
Kozo Kaibuchi ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
G Proteins ◽  
Calcium Influx ◽  
Kinase C ◽  
Rho Family ◽  
Small G Proteins

scholarly journals Phosphorylation of KLC1 modifies interaction with JIP1 and abolishes the enhanced fast velocity of APP transport by kinesin-1

2017 ◽  
Vol 28 (26) ◽  
pp. 3857-3869 ◽  
Author(s):  
Kyoko Chiba ◽  
Ko-yi Chien ◽  
Yuriko Sobu ◽  
Saori Hata ◽  
Shun Kato ◽  
...  
Keyword(s):  
Coiled Coil ◽  
Amyloid Β ◽  
Tetratricopeptide Repeat ◽  
Amyloid Β Protein ◽  
The Novel ◽  
Anterograde Transport ◽  
Interacting Protein ◽  
Protein Precursor ◽  
Kinesin Light Chain ◽  
Β Protein

In neurons, amyloid β-protein precursor (APP) is transported by binding to kinesin-1, mediated by JNK-interacting protein 1b (JIP1b), which generates the enhanced fast velocity (EFV) and efficient high frequency (EHF) of APP anterograde transport. Previously, we showed that EFV requires conventional interaction between the JIP1b C-terminal region and the kinesin light chain 1 (KLC1) tetratricopeptide repeat, whereas EHF requires a novel interaction between the central region of JIP1b and the coiled-coil domain of KLC1. We found that phosphorylatable Thr466 of KLC1 regulates the conventional interaction with JIP1b. Substitution of Glu for Thr466 abolished this interaction and EFV, but did not impair the novel interaction responsible for EHF. Phosphorylation of KLC1 at Thr466 increased in aged brains, and JIP1 binding to kinesin-1 decreased, suggesting that APP transport is impaired by aging. We conclude that phosphorylation of KLC1 at Thr466 regulates the velocity of transport of APP by kinesin-1 by modulating its interaction with JIP1b.

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