G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits.

Strathmann, Michael; Simon, Melvin I.

doi:10.1073/pnas.88.13.5582

Cited by 233 publications

(164 citation statements)

References 37 publications

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“…The Ga 12 class of heterotrimeric G-protein a-subunits, which consists of Ga 12 and Ga 13 , were cloned by homology to previously identified mammalian a-subunits (Strathmann and Simon, 1991). Ga 12 and Ga 13 have a diverse group of effectors, including RhoA (Dhanasekaran and Dermott, 1996;Kurose, 2003).…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase

et al. 2006

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“…The sequences of ␣ i2 , ␣ oA , and ␣ s were derived from rat (35), and the sequences of ␣ q and ␣ 12 were from mouse (36,37). We previously reported that exposure of H 2 O 2 induces liberation of G␤␥ from G i , leading to the activation of ERK and Akt in rat neonatal cardiomyocytes (13).…”

Section: Fig 3 Alignment Of Sequences Of Various G␣ Subunitsmentioning

confidence: 99%

Activation Mechanism of Gi and Go by Reactive Oxygen Species

Nishida¹,

Schey²,

Takagahara³

et al. 2002

Journal of Biological Chemistry

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Reactive oxygen species are proposed to work as intracellular mediators. One of their target proteins is the ␣ subunit of heterotrimeric GTP-binding proteins ( (3, 4). The increase in H 2 O 2 by platelet-derived growth factor receptor stimulation requires the activation of phosphatidylinositol 3-kinase (PI3K) and is possibly mediated by PI3K/Rac/NADPH oxidase pathway (3). The increase in H 2 O 2 was also observed by stimulation of G protein-coupled receptors such as angiotensin II (5), lysophosphatidic acid (6), and thrombin receptors (7). The generated H 2 O 2 is found to inactivate protein-tyrosine phosphatase 1B (PTP-1B) by modifying the cysteine residue located at catalytic moiety (8). However, the analysis of PTP-1B from H 2 O 2 -treated cells revealed that the cysteine residue of PTP-1B is not sulfenic acid-but glutathione-conjugated cysteine (9). Therefore, the cysteine residue of PTP-1B is at first modified by H 2 O 2 and then reacts with glutathione. This modification of cysteine leads to the inactivation of phosphatase activity of PTP-1B. Thus, the increase in H 2 O 2 indirectly changes the phosphorylation-dephosphorylation state on the tyrosine residue of proteins implicated in signal transduction (10).ROS can also be generated upon pathophysiological conditions. For instance, ROS are generated in a large amount on ischemia/reperfusion and can influence many intracellular signaling processes (11). Because the inclusion of superoxide dismutase mimics or antioxidant attenuates the cellular injury caused by ischemia/reperfusion, the prevention and mechanism of ROS generation is critical for the understanding of ischemia/reperfusion injury. The treatment with H 2 O 2 is frequently used for mimicking oxidative stress such as ischemia/ reperfusion, since H 2 O 2 freely enters cells like H 2 O (1, 2). The treatment with H 2 O 2 activates mitogen-activated protein kinase (MAPKs) such as ERK, c-Jun NH 2 -terminal kinase, and p38 MAPK and promotes or inhibits cellular injury (12).We have previously reported that the treatment of rat neonatal myocytes with H 2 O 2 activates G i and G o in a receptorindependent manner, leading to the increased activity of ERK (13). However, the molecular mechanism of G i and G o activation by H 2 O 2 is still not clear, especially about the modified amino acids. We demonstrate in the present study that H 2 O 2 is converted to more reactive species in the presence of Fe 2ϩ and modifies specific cysteine residues that exist only in G␣ i and G␣ o . The modification of two cysteine residues results in subunit dissociation of G i and increase in GTP␥S binding. . generator (KO 2 ) and PMSF were purchased from Sigma, and a singlet oxygen generator EXPERIMENTAL PROCEDURES Materials-[

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“…Binding of either ligand to distinct classes of cell surface receptors triggers a series of events that mobilize the pertussis toxin-insensitive heterotrimeric G protein subunits G␣ 12 and G␣ 13 (6,7). The intracellular targets for either G␣ subunit are a growing family of guanine nucleotide exchange factors (GEFs) (8).…”

mentioning

confidence: 99%

AKAP-Lbc Anchors Protein Kinase A and Nucleates Gα12-selective Rho-mediated Stress Fiber Formation

Diviani

Soderling

Scott

2001

Journal of Biological Chemistry

213

278

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The transmission of information from the plasma membrane to the actin cytoskeleton is essential to control a variety of dynamic cellular processes including cell shape, motility, and adherence (1). Critical mediators of these events are the Rho family small molecular weight GTPases, Rho, Rac, and Cdc42, which regulate distinct actin remodeling events. Rho is primarily responsible for the assembly of actin stress fibers and focal adhesions, and Rac controls the formation of lamellipodia, while Cdc42 induces filopodial formation (1, 2). In addition to these effects, Rho has also been implicated in a variety of other critical cellular functions including gene transcription (3,4) and progression through the cell cycle (5).Lysophosphatidic acid (LPA) and thrombin are the extracellular ligands that induce Rho signaling events (2). Binding of either ligand to distinct classes of cell surface receptors triggers a series of events that mobilize the pertussis toxin-insensitive heterotrimeric G protein subunits G␣ 12 and G␣ 13 (6, 7). The intracellular targets for either G␣ subunit are a growing family of guanine nucleotide exchange factors (GEFs) (8). These exchange factors dock with activated G␣ 12 and G␣ 13 and facilitate GTP loading of Rho. Individual cells express several Rho-GEFs, which activate distinct Rho signaling pathways (9). For example, p115 Rho-GEF interacts with G␣ 13 through a regulator of G protein signaling (RGS) domain located in the amino-terminal region of the exchange factor (10, 11). Likewise, a related module, the Lsc homology domain, governs docking of G␣ 13 to exchange factors such as PDZ Rho-GEF, KIAA0380,.A universal hallmark of exchange factors that activate GTPases of the Rho family is a conserved region of ϳ250 residues that contains a Dbl homology (DH) domain followed by a pleckstrin homology domain (9). The DH domain contains the nucleotide exchange activity, whereas the pleckstrin homology domain is thought to be involved in the subcellular localization of GEFs (2). GTPase selectivity is governed by determinants located within the DH domain that discriminate Rho-specific from Rac or Cdc42-specific exchange factors. Several families of Rho-specific exchange factors have been recognized. Members of the Lbc family were originally identified in a screen for transforming genes from human myeloid leukemias (15). OncoLbc is a 424-residue oncogenic protein with unregulated exchange factor activity that transforms NIH-3T3 cells in a Rhodependent manner (16). Subsequently, a proto-oncogenic form has been isolated with a COOH-terminal region that attenuates its transforming potential (17). More recently, a splice variant called Brx has been identified that is specifically expressed in testis and estrogen-sensitive tissues (18). Interestingly, Lbc does not possess RGS-like domains, suggesting that different mechanisms might be involved in its activation in response to extracellular signals.In this study, we demonstrate that a novel Lbc splice variant, AKAP-Lbc, is also an A-kinase-anchoring protein (...

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G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits.

Cited by 233 publications

References 37 publications

Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase

Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase

Activation Mechanism of Gi and Go by Reactive Oxygen Species

AKAP-Lbc Anchors Protein Kinase A and Nucleates Gα12-selective Rho-mediated Stress Fiber Formation

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