scholarly journals Tomato and cotton G protein beta subunit mutants display constitutive autoimmune responses

Plant Direct ◽  
2021 ◽  
Vol 5 (11) ◽  
Author(s):  
Thi Thao Ninh ◽  
Wei Gao ◽  
Yuri Trusov ◽  
Jing‐Ruo Zhao ◽  
Lu Long ◽  
...  
Keyword(s):  
G Protein ◽  
Beta Subunit

Role of the c825t polymorphic locus of G-protein beta subunit (GNBβ3) in patients with gastroesophageal reflux disease

Therapy ◽  
2021 ◽  
Vol 9_2021 ◽  
pp. 46-50
Author(s):  
Zhilina A.A. Zhilina ◽  
Lareva N.V. Lareva ◽  
Luzina E.V. Luzina ◽  
Zhigula Z.M. Zhigula Z ◽  
Tomina E.A. Tomina ◽  
...  
Keyword(s):  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
G Protein ◽  
Reflux Disease ◽  
Polymorphic Locus ◽  
Beta Subunit

The heterotrimeric G‐protein beta subunit Gpb1 controls hyphal growth under low oxygen conditions through the protein kinase A pathway and is essential for virulence in the fungus Mucor circinelloides

2020 ◽  
Vol 22 (10) ◽  
Author(s):  
Marco Iván Valle‐Maldonado ◽  
José Alberto Patiño‐Medina ◽  
Carlos Pérez‐Arques ◽  
Nancy Yadira Reyes‐Mares ◽  
Irvin Eduardo Jácome‐Galarza ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
G Protein ◽  
Hyphal Growth ◽  
Mucor Circinelloides ◽  
Beta Subunit ◽  
Low Oxygen ◽  
Heterotrimeric G Protein ◽  
Oxygen Conditions ◽  
Kinase A

scholarly journals Dominant-negative mutants of a yeast G-protein beta subunit identify two functional regions involved in pheromone signalling.

1992 ◽  
Vol 11 (13) ◽  
pp. 4805-4813 ◽  
Author(s):  
E. Leberer ◽  
D. Dignard ◽  
L. Hougan ◽  
D.Y. Thomas ◽  
M. Whiteway
Keyword(s):  
G Protein ◽  
Dominant Negative ◽  
Beta Subunit ◽  
Functional Regions ◽  
Pheromone Signalling

The Beta-Subunit Of Heterotrimeric G Proteins Harbors Gain-Of-Function Mutations In Multiple Hematologic Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2510-2510
Author(s):  
Akinori Yoda ◽  
Guillaume Adelmant ◽  
Nobuaki Shindoh ◽  
Bjoern Chapuy ◽  
Yuka Yoda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
G Protein ◽  
Kinase Inhibitors ◽  
Hematologic Malignancies ◽  
Beta Subunit ◽  
Wild Type ◽  
Gain Of Function ◽  
Alpha Subunits

Abstract To identify new oncogene alleles directly from primary tumor specimens, we generate and screen cDNA libraries from patient samples for gain-of-function alterations that can substitute for cytokine signaling in cytokine-dependent cells. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia of plasmacytoid dendritic cells with a dismal prognosis. No driver oncogenes have been identified in cases of BPDCN. Screening of a cDNA library generated from a BPDCN resulted in multiple cytokine-independent clones that expressed a full-length transcript of GNB1 with a K89E mutation. GNB1 encodes a beta subunit of the heterotrimeric G-protein, a binding complex that transduces signals from G-protein coupled receptors to multiple downstream pathways. Gain-of-function mutations have been reported in alpha subunits of the G-protein, including GNAQ/GNA11 in uveal melanoma and GNAS in pituitary tumors, however, the contributions of beta subunits to cancer remains undefined. To investigate downstream signaling from GNB1 K89E, we performed gene expression profiling and mass spectrometry (MS)-based phosphoproteomics and found significant activation of RAS/MAPK and PI3K/AKT pathways in GNB1 K89E-expressing cells compared to isogenic cells expressing wild-type GNB1. ERK and AKT activation by GNB1 K89E were confirmed by western blotting. To target GNB1 K89E signaling, we screened kinase inhibitors using a multiplex assay of small molecules and found selective sensitivity of GNB1 K89E cells to MEK and pan-PI3-kinase inhibitors. To assay the transforming effects of GNB1 K89E in vivo, we transduced GNB1 (wild-type or K89E) into bone marrow from Cdkn2a-deficient donors after 5-FU treatment and transplanted into wild-type recipients. We opted to utilize Cdkn2a-deficient donors as the loss of CDKN2A is common in cases of BPDCN. Within 4 months after transplantation, all mice (n=10) that received bone marrow transduced with GNB1 K89E developed a lethal malignancy characterized by pancytopenia and massive hepatosplenomegaly. Spleens were infiltrated by large, spindly cells with extensive dendritic projections, as well as extensive fibrosis that completely effaced the normal splenic architecture. The cells were negative for T-cell (CD2, CD3) and B-cell (CD19, B220) markers but positive for the dendritic cell/macrophage markers MAC-2 and MAC-3. Further characterization by flow cytometry demonstrated that the cells infiltrating the spleen were CD8, CD103, MHC class II, CD26, FLT3 and CD11c positive, consistent with neoplastic dendritic cells. Serial transplantation of splenic cells from five different GNB1 K89E-transplanted mice into secondary wild-type recipients resulted in 100% fatality within 50 days. We searched published datasets from exome, transcriptome and whole genome sequencing of hematologic malignancies for GNB1 mutations. We identified one case of K89E in B-cell acute lymphoblastic leukemia (ALL), four cases with I80T/N in chronic lymphocytic leukemia or B-cell lymphomas, six cases with K57E/T in myeloid neoplasms, and D76G in T-cell ALL. Expression of any of these alleles but not wild-type GNB1 was sufficient to promote cytokine-independent growth of human TF1 cells. The published structure of GNB1 (Ford et al. Science 1998) reported a small number of residues, including K57, I80 and K89 that mediate interactions with both G-alpha subunits and effector proteins. In fact, affinity purification followed by MS using tagged GNB1 (wild-type, I80T and K89E) demonstrated that, unlike wild-type GNB1, the GNB1 mutants fail to bind distinct Gα subunits. The repertoire of protein interactors, which includes potential G protein effectors, also differed between different GNB1 alleles. Thus, gain-of-function mutations in GNB1 occur across a broad range of hematologic malignancies, modify essential interaction G-protein subunit interactions, can drive in vivo transformation, and activate targetable downstream kinases. Disclosures: Tyner: Incyte Corporation: Research Funding.

scholarly journals Molecular cloning of beta 3 subunit, a third form of the G protein beta-subunit polypeptide.

1990 ◽  
Vol 87 (6) ◽  
pp. 2329-2333 ◽  
Author(s):  
M. A. Levine ◽  
P. M. Smallwood ◽  
P. T. Moen ◽  
L. J. Helman ◽  
T. G. Ahn
Keyword(s):  
Molecular Cloning ◽  
G Protein ◽  
Beta Subunit ◽  
Subunit A

Overexpression of the STE4 gene leads to mating response in haploid Saccharomyces cerevisiae

1990 ◽  
Vol 10 (1) ◽  
pp. 217-222
Author(s):  
M Whiteway ◽  
L Hougan ◽  
D Y Thomas
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
G Protein ◽  
Gene Product ◽  
Beta Subunit ◽  
Yeast Cells ◽  
Pheromone Response ◽  
Mating Pheromone ◽  
Cycle Arrest

The STE4 gene of Saccharomyces cerevisiae encodes the beta subunit of the yeast pheromone receptor-coupled G protein. Overexpression of the STE4 protein led to cell cycle arrest of haploid cells. This arrest was like the arrest mediated by mating pheromones in that it led to similar morphological changes in the arrested cells. The arrest occurred in haploid cells of either mating type but not in MATa/MAT alpha diploids, and it was suppressed by defects in genes such as STE12 that are needed for pheromone response. Overexpression of the STE4 gene product also suppressed the sterility of cells defective in the mating pheromone receptors encoded by the STE2 and STE3 genes. Cell cycle arrest mediated by STE4 overexpression was prevented in cells that either were overexpressing the SCG1 gene product (the alpha subunit of the G protein) or lacked the STE18 gene product (the gamma subunit of the G protein). This finding suggests that in yeast cells, the beta subunit is the limiting component of the active beta gamma element and that a proper balance in the levels of the G-protein subunits is critical to a normal mating pheromone response.

scholarly journals Genetic identification of residues involved in association of alpha and beta G-protein subunits.

1994 ◽  
Vol 14 (5) ◽  
pp. 3223-3229 ◽  
Author(s):  
M Whiteway ◽  
K L Clark ◽  
E Leberer ◽  
D Dignard ◽  
D Y Thomas
Keyword(s):  
G Protein ◽  
Protein A ◽  
Beta Subunit ◽  
Yeast Cells ◽  
Genetic Identification ◽  
Alpha Subunit ◽  
Protein Subunit ◽  
Direct Role ◽  
Subunit Dissociation ◽  
Allele Specific

The GPA1, STE4, and STE18 genes of Saccharomyces cerevisiae encode the alpha, beta, and gamma subunits, respectively, of a G protein involved in the mating response pathway. We have found that mutations G124D, W136G, W136R, and delta L138 and double mutations W136R L138F and W136G S151C of the Ste4 protein cause constitutive activation of the signaling pathway. The W136R L138F and W136G S151C mutant Ste4 proteins were tested in the two-hybrid protein association assay and found to be defective in association with the Gpa1 protein. A mutation at position E307 of the Gpa1 protein both suppresses the constitutive signaling phenotype of some mutant Ste4 proteins and allows the mutant alpha subunit to physically associate with a specific mutant G beta subunit. The mutation in the Gpa1 protein is adjacent to the hinge, or switch, region that is required for the conformational change which triggers subunit dissociation, but the mutation does not affect the interaction of the alpha subunit with the wild-type beta subunit. Yeast cells constructed to contain only the mutant alpha and beta subunits mate and respond to pheromones, although they exhibit partial induction of the pheromone response pathway. Because the ability of the modified G alpha subunit to suppress the Ste4 mutations is allele specific, it is likely that the residues defined by this analysis play a direct role in G-protein subunit association.

Multiple forms of the G protein-related beta subunit in Daudi lymphoblastoid cells

1993 ◽  
Vol 35 (3) ◽  
pp. 255-263
Author(s):  
Ching-Kow E. Lin ◽  
John S. Kaptein ◽  
David Guoqing Gu ◽  
Cosmas I. Kalunta ◽  
Pramod M. Lad
Keyword(s):  
G Protein ◽  
Beta Subunit ◽  
Multiple Forms ◽  
Lymphoblastoid Cells
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