Small G proteins and their regulators in cellular signalling

Csépányi-Kömi, Roland; Lévay, Magdolna; Ligeti, Erzsébet

doi:10.1016/j.mce.2011.11.005

Cited by 33 publications

(39 citation statements)

References 145 publications

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“…The situation is especially complex in case of the Rho subfamily, where the potential GAPs outnumber the smgs by a factor of 3 or 4. 3 The large number of the regulatory proteins, their varied domain structure and different substrate specificity raise a long series of questions. This review discusses the complexity of the Rho family of GAPs revealed in neutrophilic granulocytes.…”

Section: Introductionmentioning

confidence: 99%

The neglected terminators: Rho family GAPs in neutrophils

Csépányi-Kömi

Pásztor

Bartos

et al. 2018

Eur J Clin Investigation

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Background: GTPase-activating proteins (GAPs) accelerate the rate of hydrolysis of GTP bound to small GTPases, thereby limiting the prevalence and concentration of the active, GTP-bound form of these proteins. The large number of potential GAPs acting on members of the Rho family of small GTPases raises the question of specificity or redundancy. Results: In this review, we summarize experimental data obtained on the role of Rho family GAPs in neutrophils, highlight cases where more than one GAP is involved in a physiological function and show examples that GAPs can be involved not only in termination but also in initiation of cellular processes. We demonstrate that the expression-level regulation of GAPs may also occur in shortliving cells such as neutrophils. Finally, we provide insight into the existence and structure of molecular complexes in which Rho family GAPs are involved. Conclusion: GAPs play more complex and varied roles than being simple terminators of cellular processes. K E Y W O R D SGTPase activating proteins, Rho-family small GTPases, neutrophils

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Section: Introductionmentioning

confidence: 99%

The neglected terminators: Rho family GAPs in neutrophils

Csépányi-Kömi

Pásztor

Bartos

et al. 2018

Eur J Clin Investigation

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“…Some elements of this SNARE complex can also act as negative regulators of membrane fusion: as is the case during sperm exocytosis, where -SNAP prevents docking of the acrosome by sequestering monomeric Syntaxin . As mentioned above, the small GTPases involved in exocytosis are regulated by switching between an active (GTP-bound) and inactive (GDP-bound) state (Ali & Seabra, 2005;Barr & Lambright, 2010;Csepanyi-Komi, et al, 2011;Stenmark, 2009;Uno, et al, 2010) (Figure 1). This exchange between two states is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) (Csepanyi-Komi, et al, 2011).…”

Section: Exocyst Snare Complexes and Membrane Fusion Machinerymentioning

confidence: 97%

“…As mentioned above, the small GTPases involved in exocytosis are regulated by switching between an active (GTP-bound) and inactive (GDP-bound) state (Ali & Seabra, 2005;Barr & Lambright, 2010;Csepanyi-Komi, et al, 2011;Stenmark, 2009;Uno, et al, 2010) (Figure 1). This exchange between two states is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) (Csepanyi-Komi, et al, 2011). GEF proteins activate GTPases by a mechanism involving the destabilization of the interaction between the GEF and guanosine di-phosphate (GDP), resulting in the fast release of the GDP and generation of a nucleotide-free GTPase-GEF intermediary complex (Liao, et al, 2008).…”

Section: Exocyst Snare Complexes and Membrane Fusion Machinerymentioning

confidence: 97%

“…Emerging data highlights that small GTPases of the Ras super-family, including the Ras homologous (Rho), Ras-associated binding proteins (Rabs), adenosine ribosylation factors (Arfs), and Ras-like proteins (Ral) subfamilies, are involved in regulating distinct steps during exocytosis, some of which are mediated via interaction with the exocyst (reviewed in (Csepanyi-Komi, et al, 2011;Hutagalung & Novick, 2011;Segev, 2011)). Thus, there appears to be stage-specific requirements for small GTPase subfamily members during exocytosis (Figure 1).…”

Section: Small Gtpases As Regulators Of Exocytosismentioning

confidence: 99%

“…Once activated by GEFs, the small GTPases (Rho, Rab, Arf, and Ral) translocate to their destination membrane in order to carry out their specific function (Csepanyi-Komi, et al, 2011). In exocytosis, the GEFs identified so far control the function of members of three of the GTPase families, the Rabs, Rals, and the Rhos.…”

Section: Exocyst Snare Complexes and Membrane Fusion Machinerymentioning

confidence: 99%

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Cyclic nucleotide‐dependent inhibitory signaling interweaves with activating pathways to determine platelet responses

Nagy

Smolenski

2018

Research and Practice in Thrombosis and Haemostasis

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Platelets are regulated by extracellular cues that impact on intracellular signaling. The endothelium releases prostacyclin and nitric oxide which stimulate the synthesis of cyclic nucleotides cAMP and cGMP leading to platelet inhibition. Other inhibitory mechanisms involve immunoreceptor tyrosine‐based inhibition motif‐containing receptors, intracellular receptors and receptor desensitization. Inhibitory cyclic nucleotide pathways are traditionally thought to represent a passive background system keeping platelets in a quiescent state. In contrast, cyclic nucleotides are increasingly seen to be dynamically involved in most aspects of platelet regulation. This review focuses on crosstalk between activating and cyclic nucleotide‐mediated inhibitory pathways highlighting emerging new hub structures and signaling mechanisms. In particular, interactions of plasma membrane receptors like P2Y12 and GPIb/IX/V with the cyclic nucleotide system are described. Furthermore, differential regulation of the RGS18 complex, second messengers, protein kinases, and phosphatases are presented, and control over small G‐proteins by guanine‐nucleotide exchange factors and GTPase‐activating proteins are outlined. Possible clinical implications of signaling crosstalk are discussed.

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Small G proteins and their regulators in cellular signalling

Cited by 33 publications

References 145 publications

The neglected terminators: Rho family GAPs in neutrophils

The neglected terminators: Rho family GAPs in neutrophils

Molecular Machinery Regulating Exocytosis

Cyclic nucleotide‐dependent inhibitory signaling interweaves with activating pathways to determine platelet responses

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