Signaling by the G Class of G Proteins

Dhanasekaran, N.; Dermott, Jonathan M.

doi:10.1016/0898-6568(96)00048-4

Cited by 130 publications

(95 citation statements)

References 65 publications

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“…Activated Ga 12/13 in turn binds to and activate rhoGEFs Suzuki et al, 2003), which then activate RhoA (Dhanasekaran and Dermott, 1996;Kurose, 2003). Ga 13 has been directly implicated in GPCRstimulated cell migration (Offermanns et al, 1997;Radhika et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

“…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). Ga 13 was first implicated in GPCR-stimulated cell migration because Ga 13 null murine embryonic fibroblasts have impaired chemokinesis to thrombin (Offermanns et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

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 response was dose-dependent, and was greater for rac* than rac. For comparison, wild-type and activated versions of the heterotrimeric G-protein Ga13, which is oncogenic (Dhanasekaran and Dermott, 1996;VoynoYasenetskaya et al, 1994) and is thought to regulate rac-dependent signaling pathways (Voyno-Yasenetskaya et al, 1996;Vara Prasad et al, 1995), were also tested. Ga13* induced a response very similar in magnitude to rac*.…”

Section: Resultsmentioning

confidence: 99%

“…Rac(7) and ras(7) are each dominant negative mutants which contain the mutation T17N, rendering these proteins unable to bind GTP ( see Feig and Cooper 1988) pathways (Clapham and Neer, 1993). The heterotrimeric G-proteins Gaq, Ga12 and Ga13 are each capable of transforming NIH3T3 cells (Dhanasekaran and Dermott, 1996;Voyno-Yasenetskaya et al, 1994;Chan et al, 1993;Xu et al, 1993;Jiang et al, 1993;Kalinec et al, 1992) and we have previously shown that Gaq but not Ga12 is responsible for transducing m5-induced proliferative responses in NIH3T3 cells (Burstein et al, 1995b;. It has been recently shown that GTPase de®cient mutants of Gaq, Ga12 and Ga13 activate the JNK pathway (VoynoYasenetskaya et al, 1996;Vara Prasad et al, 1995) and we have found that Gaq, Ga12 and Ga13 can each induce proliferative responses in R-SAT TM (Figure 1 and see Burstein et al, 1997).…”

Section: Alpha1bmentioning

confidence: 99%

The ras-related GTPase rac1 regulates a proliferative pathway selectively utilized by G-protein coupled receptors

et al. 1998

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Ras and rac are each members of the superfamily of monomeric GTPases and both function as molecular switches to link cell-surface signals to intracellular responses. Using a novel assay of cellular proliferation called R-SAT TM (Receptor Selection and Ampli®cation Technology), we examined the roles of ras and rac in mediating the proliferative responses to a variety of cellsurface receptors. Activated, wild-type and dominantnegative mutants of rac and ras were tested for their e ects on cellular proliferation either alone or in combination with receptors. Activated rac (rac Q61L, henceforth rac*) and ras (ras G12V, henceforth ras*) each induced strong proliferative responses. Dominantnegative rac (rac T17N, henceforth rac (7)) dramatically suppressed proliferative responses to G-protein coupled receptors (GPCR's) including the m5 muscarinic receptor and the a1B adrenergic receptor. In contrast, rac(7) had little or no e ect upon responses to the tyrosine kinase receptor TrkC, and only partially suppressed responses to the Janus kinase (JAK/STAT) linked granulocyte macrophage colony stimulating factor (GM-CSF) receptor. Dominant-negative ras (ras T17N, henceforth ras(7)) blocked the proliferative responses to all of the tested receptors. Compared to rac(7) and ras(7), wild-type rac and ras had only modest e ects on the tested receptors. Overall these results demonstrate that rac mediates the proliferative e ects of G-protein coupled receptors through a pathway that is distinct from the proliferative signaling pathway utilized by tyrosine kinase linked and JAK-linked receptors.

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“…Although intracellular localizations of thrombin and LPA receptors are not yet known, selective targeting of G proteins and receptors to either lipid raft fraction or other fraction may determine the selective coupling. G␣ 12 and G␣ 13 mostly display mutual downstream signal transductions, such as RhoA activation and serum response factor activation (2,16). Recently, a variety of downstream effectors or interacting proteins of the G␣ 12 family have been identified, including Rho guanine nucleotide exchange factors, cadherin, and PP5, and they interact with both G␣ 12 and G␣ 13 (10,11,14), suggesting that downstream signal transduction pathways of G␣ 12 and G␣ 13 are highly overlapped.…”

Section: Fig 2 Selective Activations Of G␣mentioning

confidence: 99%

N-terminal Short Sequences of α Subunits of the G12Family Determine Selective Coupling to Receptors

Yamaguchi¹,

Katoh

Negishi

2003

Journal of Biological Chemistry

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sequence homology of their ␣ subunits (1). The G 12 family is defined by G␣ 12 and G␣ 13 , and they share 67% amino acid sequence identity (2). Active forms of G␣ 12 and G␣ 13 induce several biological responses via activation of Rho, a major downstream common target for G␣ 12 and G␣ 13 , including stimulation of stress fiber formation and focal adhesion assembly (3), induction of neurite retraction (4), induction of apoptosis (5), transformation of fibroblasts (6), activation of phospholipase D (7), inhibition of Ca 2ϩ -dependent exocytosis (8), and activation of c-Jun N-terminal kinase (9). Recently, several proteins that interact with both G␣ 12 and G␣ 13 have been identified, including p115, a Rho guanine nucleotide exchange factor (10), cadherin (11), and radixin (12). Therefore, G␣ 12 and G␣ 13 are thought to transduce mutual downstream signaling through these effectors. In contrast, a variety of GPCRs appear to selectively couple to G␣ 12 or G␣ 13 (13). For example, thrombin and lysophosphatidic acid (LPA) have been shown to induce stress fiber formation via G␣ 12 and G␣ 13 , respectively, by using dominant negative mutants of G␣ 12 and G␣ 13 (13). However, this receptor-G protein coupling is not directly evaluated.Recently, we demonstrated that G␣ 12 and G␣ 13 interact with Ser/Thr phosphatase type 5 (PP5) through its tetratricopeptide repeat (TPR) domain and stimulate its phosphatase activity (14). In this study, we developed a novel assay to evaluate the activities of G␣ 12 and G␣ 13 by using glutathione S-transferase (GST)-fused TPR domain of PP5 (GST-TPR), taking advantage of the property that GST-TPR strongly interacts with active forms of G␣ 12 and G␣ 13 . By using this assay, we showed selective activations of G␣ 12 by thrombin and G␣ 13 by LPA, and found that N-terminal short sequences of G␣ 12 and G␣ 13 determine these selective activations. EXPERIMENTAL PROCEDURESMaterials-Agents obtained and commercial sources were as follows: thrombin and LPA, Sigma; rabbit polyclonal anti-G␣ 12 and anti-G␣ 13 antibodies and mouse monoclonal anti-RhoA antibody, Santa Cruz Biotechnology, Inc.; horseradish peroxidase-conjugated goat anti-mouse immunoglobulin G antibody and horseradish peroxidase-conjugated swine anti-rabbit immunoglobulin G antibody, DAKO; and Chemiluminescence ECL Western blotting system, Amersham Biosciences. GSTfused proteins were purified from Escherichia coli as described previously (8,14). The TPR domain used for GST-TPR is a splicing variant of rat PP5 that contains residues 9 -122 following a new short coding region (12 amino acids; SRALGMGQLPAP) (14). The nucleotide sequence of this TPR variant is available from GenBank TM /EMBL/DDBJ under accession number AB101661.Plasmid Constructions-cDNAs of wild-type G␣ 12 and G␣ 13 (G␣ 12 WT and G␣ 13 WT), and their constitutively active mutants of G␣ 12 (G␣ 12 Q229L, G␣ 12 QL) and G␣ 13 (G␣ 13 Q226L, G␣ 13 QL) were obtained as described previously (4,14). To generate chimeric cDNA of G␣ 13 substituted with the N-terminal short sequence of G␣ 12 ...

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Signaling by the G Class of G Proteins

Cited by 130 publications

References 65 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

The ras-related GTPase rac1 regulates a proliferative pathway selectively utilized by G-protein coupled receptors

N-terminal Short Sequences of α Subunits of the G12Family Determine Selective Coupling to Receptors

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