The Ras superfamily of GTPases
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Macara, Ian G.; Lounsbury, Karen M.; Richards, Shane A.; McKiernan, C J; Bar–Sagi, Dafna

doi:10.1096/fasebj.10.5.8621061

Cited by 238 publications

(155 citation statements)

References 37 publications

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“…It encodes the first known regulator of the Rho family of small GTPases that binds to a tyrosine kinase (21,28). The Rho family belongs to the RAS superfamily and consists of five distinct types of GTP-binding proteins: RhoA, RhoB, RhoC, and RhoD; Rac1 and Rac2; Cdc42 and G25K; TC10, and RhoG (28,33,34). Rho, Rac, and Cdc42 regulate the organization of the actin cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q

Borkhardt

Bojesen

Haas

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

113

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We have isolated the human GRAF gene (for GTPase regulator associated with the focal adhesion kinase pp125 FAK ). This gene was fused with MLL in a unique t(5;11)(q31;q23) that occurred in an infant with juvenile myelomonocytic leukemia. GRAF encodes a member of the Rho family of the GTPase-activating protein (GAP) family. On the protein level, it is 90% homologous to the recently described chicken GRAF gene that functions as a GAP of RhoA in vivo and is thus a critical component of the integrin signaling transduction pathway. The particular position of the human GRAF gene at 5q31 and the proposed antiproliferative and tumor suppressor properties of its avian homologue suggest that it also might be pathogenetically relevant for hematologic malignancies with deletions of 5q. To investigate this possibility, we sequenced 4 -5 individual cDNA clones from 13 cases in which one allele of GRAF was deleted. We found point mutations within the GAP domain of the second GRAF allele in one patient. In two additional patients we found an insertion of 52 or 74 bp within the GRAF cDNA that generates a reading frame shift followed by a premature stop codon. GRAF maps outside the previously defined commonly deleted 5q31 region. Nevertheless, inactivation of both alleles in at least some cases suggests that deletions and mutations of the GRAF gene may be instrumental in the development and progression of hematopoeitic disorders with a del(5q).

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Section: Discussionmentioning

confidence: 99%

The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q

Borkhardt

Bojesen

Haas

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

113

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“…The Ras family can be subdivided based on homologies within the effector domains, with Rap, R-Ras, Ral, RheB, M-Ras, comprising one subfamily, and H-Ras, K-Ras and N-Ras comprising another. 63 Activation of Ras involves a switch from a guanosine diphosphate (GDP)-bound state to guanosine triphosphate (GTP)-bound state. Ras activation is regulated by GTPase activating proteins (GAPs) that augment the hydrolysis of GTP to GDP and by guanine nucleotide exchange factors (GEFs) that catalyze the GDP/GTP exchange.…”

Section: Ras Signalingmentioning

confidence: 99%

“…Ras activation is regulated by GTPase activating proteins (GAPs) that augment the hydrolysis of GTP to GDP and by guanine nucleotide exchange factors (GEFs) that catalyze the GDP/GTP exchange. 63,64 Activated Ras is localized to the inner surface of the plasma membrane and this localization is dependent on post-translational modifications including farnesylation of a cysteine residue near the carboxy terminus, proteolytic cleavage of the C-terminal amino acids and carboxymethylation of the farnesylated cysteine. 64 In addition, cysteine residues upstream of the farnesylated cysteine are reversibly palmitoylated.…”

Section: Ras Signalingmentioning

confidence: 99%

Signal transduction pathways that contribute to myeloid differentiation

Miranda

Johnson

2007

Leukemia

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The production of mature, differentiated myeloid cells is regulated by the action of hematopoietic cytokines on progenitor cells in the bone marrow. Cytokines drive the process of myeloid differentiation by binding to specific cell-surface receptors in a stage-and lineage-specific manner. Following the binding of a cytokine to its cognate receptor, intracellular signal-transduction pathways become activated that facilitate the myeloid differentiation process. These intracellular signaling pathways may promote myelopoiesis by stimulating expansion of a progenitor pool, supporting cellular survival during the differentiation process, or by directly driving the phenotypic changes associated with differentiation. Ultimately, pathways that drive the differentiation process converge on myeloid transcription factors, including PU.1 and the C/EBP family, that are critical for differentiation to proceed. While much is known about the cytokines, cytokine receptors and transcription factors that regulate myeloid differentiation, less is known about the precise roles that specific signaling mediators play in promoting myeloid differentiation. Recently, however, the application of novel pharmacologic inhibitors, siRNA strategies, and transgenic and knockout models has begun to shed light on the involvement and function of signaling pathways in normal myeloid differentiation. This review will discuss the roles that key signaling pathways and mediators play in myeloid differentiation.

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“…Monomeric G proteins (small G proteins) [113,172], and heterotrimeric G proteins [24,172] have been described as the two main families of signal transduction-related proteins that bind and hydrolyze guanine nucleotides. Heterotrimeric G proteins are formed by three subunits ( , , and ).…”

Section: Heterotrimeric G Proteinsmentioning

confidence: 99%

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

González-Maeso

Meana²

2006

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Mood disorders such as major depression and bipolar disorder are common, severe, chronic and often lifethreatening illnesses. Suicide is estimated to be the cause of death in up to approximately 10-15% of individuals with mood disorders. Alterations in the signal transduction through G protein-coupled receptor (GPCR) pathways have been reported in the etiopathology of mood disorders and the suicidal behavior. In this regard, the implication of certain GPCR subtypes such as 2A -adrenoceptor has been repeatedly described using different approaches. However, several discrepancies have been recently reported in density and functional status of the heterotrimeric G proteins both in major depression and bipolar disorder. A compilation of the most relevant research topics about the implication of heterotrimeric G proteins in the etiology of mood disorders (i.e., animal models of mood disorders, studies in peripheral tissue of depressive patients, and studies in postmortem human brain of suicide victims with mood disorders) will provide a broad perspective of this potential therapeutic target field. Proposed causes of the discrepancies reported at the level of G proteins in postmortem human brain of suicide victims will be discussed.

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The Ras superfamily of GTPases ¹

Cited by 238 publications

References 37 publications

The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q

The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q

Signal transduction pathways that contribute to myeloid differentiation

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

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The Ras superfamily of GTPases 1

Cited by 238 publications

References 37 publications

The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q

The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q

Signal transduction pathways that contribute to myeloid differentiation

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

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Resources

About

The Ras superfamily of GTPases ¹