Role of heterotrimeric G proteins in polarized membrane transport

1993 ◽  
Vol 1993 (Supplement 17) ◽  
pp. 27-32 ◽  
Author(s):  
S. W. Pimplikar ◽  
K. Simons
Keyword(s):  
Membrane Transport ◽  
G Proteins ◽  
Heterotrimeric G Proteins

scholarly journals Heterotrimeric G-Proteins Are Indispensable for FLT3-ITD autophosphorylation and Oncogenic Function

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2712-2712
Author(s):  
Maike Rehage ◽  
Susanne Wingert ◽  
Nadine Haetscher ◽  
Sabrina Bothur ◽  
Hubert Serve ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
G Protein ◽  
G Proteins ◽  
B Cell Lymphoma ◽  
Physical Interaction ◽  
Heterotrimeric G Proteins ◽  
Leukemic Transformation ◽  
Hematopoietic Stem ◽  
Oncogenic Function

Abstract Heterotrimeric G-proteins transmit signals of G-protein coupled receptors and regulate many basic cellular functions. However, their role in normal and malignant hematopoietic stem cells remains obscure. Activating mutations in the heterotrimeric G-protein Gaq were found in various cancers and its expression is enhanced in diffuse large B-cell lymphoma and T-ALL. Our previous data suggested the involvement of heterotrimeric G-proteins in Flt3-ITD-mediated leukemic transformation. FMS-like tyrosine kinase 3 with internal tandem duplication (FLT3-ITD) is a frequent oncoprotein in acute myeloid leukemia causing constitutive active STAT5 signaling. Here, we investigated a novel role of Gaq in Flt3-ITD-induced leukemic transformation. We could show that Gaq is indispensable for aberrant FLT3-ITD activation and oncogenic function as Gaq activity is necessary to maintain the autophosphorylation of FLT3-ITD. Gaq abrogation resulted in diminished cell proliferation and colony formation as well as delayed leukemogenesis in vivo of Flt3-ITD leukemic cells. Importantly, the growth inhibition could be rescued by addition of IL3 and did not occur in the presence of FLT3 ligand-activated FLT3 wildtype receptor, demonstrating the specificity of Gaq requirement for FLT3-ITD oncogenic signaling. Interestingly, co-immunoprecipitations revealed a direct physical interaction between FLT3-ITD and Gaq which did not require phosphorylation of the receptor tyrosine kinase. Hence, FLT3-ITD hyperphosphorylation seems to be rather a consequence of the interaction than a prerequisite. Flt3-ITD-induced transformation of murine hematopoietic stem/progenitor cells (HSPCs) strictly depended on the presence of Gaq, and the ablation of Gaq/11 in transplanted Flt3-ITD-transduced HSPCs from conditional Gaq/11 double knock-out mice delayed leukemic burden. These findings of an unexpected, yet critical, role of Gaq place the molecule as an important target for antileukemic strategies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Heterotrimeric G Proteins of the Gq/11 Family Are Crucial for the Induction of Maternal Behavior in Mice

2004 ◽  
Vol 24 (18) ◽  
pp. 8048-8054 ◽  
Author(s):  
Nina Wettschureck ◽  
Alexandra Moers ◽  
Tuula Hamalainen ◽  
Thomas Lemberger ◽  
Günther Schütz ◽  
...  
Keyword(s):  
G Proteins ◽  
Maternal Behavior ◽  
Motor Behavior ◽  
Oxytocin Receptor ◽  
Lateral Septum ◽  
Heterotrimeric G Proteins ◽  
Bed Nucleus ◽  
The Central Nervous System ◽  
Gland Function

ABSTRACT Heterotrimeric G proteins of the Gq/11 family transduce signals from a variety of neurotransmitter receptors and have therefore been implicated in several functions of the central nervous system. To investigate the potential role of Gq/11 signaling in behavior, we generated mice which lack the α-subunits of the two main members of the Gq/11 family, Gαq and Gα11, selectively in the forebrain. We show here that forebrain Gαq/11-deficient females do not display any maternal behavior such as nest building, pup retrieving, crouching, or nursing. However, olfaction, motor behavior and mammary gland function are normal in forebrain Gαq/11-deficient females. We used c-fos immunohistochemistry to investigate pup-induced neuronal activation in different forebrain regions and found a significant reduction in the medial preoptic area, the bed nucleus of stria terminalis, and the lateral septum both in postpartum females and in virgin females after foster pup exposure. Pituitary function, especially prolactin release, was normal in forebrain Gαq/11-deficient females, and activation of oxytocin receptor-positive neurons in the hypothalamus did not differ between genotypes. Our findings show that Gq/11 signaling is indispensable to the neuronal circuit that connects the perception of pup-related stimuli to the initiation of maternal behavior and that this defect cannot be attributed to either reduced systemic prolactin levels or impaired activation of oxytocin receptor-positive neurons of the hypothalamus.

Role of heterotrimeric G-proteins in epidermal growth factor signalling

1995 ◽  
Vol 7 (4) ◽  
pp. 303-311 ◽  
Author(s):  
Ignasi Ramírez ◽  
Francesc Tebar ◽  
Montserrat Grau ◽  
Maria Soley
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
G Proteins ◽  
Heterotrimeric G Proteins ◽  
Growth Factor Signalling ◽  
Epidermal Growth

scholarly journals Role of heterotrimeric G proteins in platelet activation and clot formation in platelets treated with integrin αIIbβ3 inhibitor

Platelets ◽  
2017 ◽  
Vol 29 (3) ◽  
pp. 265-269 ◽  
Author(s):  
Ivan Budnik ◽  
Boris Shenkman ◽  
Hagit Hauschner ◽  
Isaac Zilinsky ◽  
Naphtali Savion
Keyword(s):  
G Proteins ◽  
Platelet Activation ◽  
Clot Formation ◽  
Heterotrimeric G Proteins ◽  
Integrin Αiibβ3

scholarly journals Role of heterotrimeric G proteins in membrane traffic.

1992 ◽  
Vol 3 (12) ◽  
pp. 1317-1328 ◽  
Author(s):  
M Bomsel ◽  
K Mostov
Keyword(s):  
G Proteins ◽  
Membrane Traffic ◽  
Heterotrimeric G Proteins

scholarly journals Functional Gene Group Analysis Reveals a Role of Synaptic Heterotrimeric G Proteins in Cognitive Ability

2010 ◽  
Vol 86 (2) ◽  
pp. 113-125 ◽  
Author(s):  
Dina Ruano ◽  
Gonçalo R. Abecasis ◽  
Beate Glaser ◽  
Esther S. Lips ◽  
L. Niels Cornelisse ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
G Proteins ◽  
Group Analysis ◽  
Functional Gene ◽  
Heterotrimeric G Proteins ◽  
Gene Group

scholarly journals The role of heterotrimeric G proteins in the control of symbiosis development in legume plants

2020 ◽  
Vol 23 ◽  
pp. 03004
Author(s):  
Andrey D. Bovin ◽  
Irina V. Leppyanen ◽  
Olga A. Pavlova ◽  
Elena A. Dolgikh
Keyword(s):  
Gene Expression ◽  
G Proteins ◽  
Heterotrimeric G Proteins ◽  
Subunit Gene ◽  
Gene Suppression ◽  
Gamma Subunits ◽  
Genes Encoding ◽  
Specific Proteins ◽  
Alpha Beta

Heterotrimeric G proteins are involved in the regulation of signaling pathways in eukaryotes. Previously, the data about possible participation of heterotrimeric G proteins in the regulation of nodulation in legumes were obtained, however, specific proteins, their composition and role in this process remain poorly understood. In this work searching of the genes encoding the alpha, beta, and gamma subunits of heterotrimeric G proteins based on an analysis of the Pisum sativum L. genome was performed, as well as the dynamics of the gene expression encoding the particular subunits of G proteins in the process of symbiosis was studied. In addition, a significant effect of beta 1-subunit gene suppression by RNA interference on the nodulation process was revealed.

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