RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1)

Identity

Other names	CDC25
	CDC25L
	GNRP
	GRF1
	GRF55
	H-GRF55
	PP13187
Hugo	RASGRF1
Location	15q25.1

DNA/RNA

Note	Differential imprinted methylation of the paternal and maternal alleles in neonatal brain. The methylation of promoter of the paternal allele prevents the binding and gene silencing caused by CTCF in the unmethylated maternal allele.
Description	128.44 Kb, 28 exons.
Transcription	mRNA size: 4022 bases.

Protein

	The diagram shows the functional modules present in Ras-GRF1. The flanking amino-acid limits shown correspond to the human protein. Arrows indicate the phosphorylation sites that have been characterized and, in brackets, the kinases responsible. It should be noted that Ras-GRF1 has approximately 83 predicted phosphorylation sites; 63 serines, 19 threonines and 11 tyrosines. The regions essential for inducing GDP/GTP release in Rac and Ras GTPases are underlined. Other interacting proteins and the regions involved in such interactions are shown by broken lines. PM, Plasma Membrane; CaM, Calmodulin. The descriptions of Ras-GRF domains can be found in the text.

Note	In the early 90s, several groups identified in murine brain extracts, a protein of a molecular weight between 100-160 kDa, named Ras-GRF (Ras-Guanine nucleotide Releasing Factor) and Cdc25Mm, based on its ability to induce GDP release in p21ras and on its high homology with the Sacharomyces cerevisiae gene CDC25, whose deficiency it could rescue.
Description	Ras-GRF1 is a protein that contains multiple modular motifs. The Ras-GEF region, includes the Cdc25 domain which exhibits guanine nucleotide exchange factor (GEF) activity towards the Ras family GTPase and a REM (Ras Exchanger-stabilization Motif) domain, responsible for the stabilization of the core of the Cdc25 domain. Separating these domains, there is a region rich in proline, glutamic acid, serine and treonine aminoacids (PEST) that constitutes a hypothetical target for proteolysis. Ras-GRF1 also possesses: two pleckstrin-homology (PH) domains, which have been suggested to interact with polyphosphoinositides and other types of phospholipids and may play some role in Ras-GRF1 interactions with membranes: the α-helical coiled-coil (CC) motif plays a role in protein-protein interactions; a Isoleucine-Glutamin (IQ) domain, which binds Calmodulin and is responsible for the calcium-dependent activation of Ras-GRF1; and a dbl-homology (DH) region, which exhibits GEF activity towards Rho family GTPases, in particular Rac-1. The DH domain also mediates in Ras-GRF dimerization that ensues upon activation. The DH domain and the second PH domain constitute the catalytic module, archetypically present in all Rho-GEFs, which entails nucleotide exchange activity over Rho family GTPases. Ras-GRF1, along with Ras-GRF2 and Sos, are the only known exchange factors that combine Rho and Ras exchanger activity in the same protein.
Expression	Ras-GRF1 is fundamentally expressed in the central nervous system and, at a reduced level, also in the spinal cord. It is more abundant in hippocampus, some deep nuclei, neocortex, and the granule cell layer of the anterior lobules of the cerebellum. Its expression is low during embryonary development and increased drastically in the first days after birth. Its presence has also been reported in pancreatic beta cells. Alternative splicing variants are expressed in brain, lung, pancreas, as well as several tumour cell lines.
Localisation	By immunofluorescence, Ras-GRF1 exhibits a predominant cytoplasmic distribution, particularly at the perinuclear area, and mostly excluded from lamelipodia and peripheral structures. However, significant amounts are also associated to the plasma-membrane and in the endoplasmic reticulum, but not the Golgi Apparatus. Such a distribution can be ascertained by biochemical fractionation, which shows Ras-GRF1 in both soluble and particulate fractions, its proportions vary depending on the cell type. Its association with membranes does not increase upon activation. In addition, it is also remarkably present in the synaptic junctions of mature neurons.
Function	The main function of Ras-GRF1, relays in its ability to activate GTPases in response to signals emanating from G protein-coupled receptors and from calcium fluxes. Ras-GRF1 also plays an important role linking signals from AMPA and NMDA receptors to the MAPK/ERK cascade in mature neurons. Initially, it was believed that Ras-GRF1 was unresponsive to signals generated by tyrosine kinase receptors, but lately, it has been demonstrated that Trk-family receptors can phosphorylate and directly associate to Ras-GRF1. Ras-GRF1 acts as a bifunctional protein with the ability to activate both Ras and Rac-1 GTPases. In vitro, Ras-GRF1 can activate H-Ras, K-Ras and N-Ras GTPases, but in vivo, its specificity is reduced to H-Ras, probably as a consequence of microlocalization processes taking place. Ras-GRF1 can also activate the R-Ras subfamily GTPases, namely: , TC21 and M-Ras. On the other hand, Ras-GRF1 acts as a Rac-GEF when activated in a Gβγ-dependent fashion. Another Rho-family GTPase, Cdc42, exhibits a functional relationship with Ras-GRF1 activity, by being capable of negatively regulating Ras-GRF1 Ras-GEF functions. The mechanisms whereby such a regulation is achieved are yet unknown. Ras-GRF1 knock-out mice are viable and show no major developmental alterations. They do show some mental restrains: they are severely impaired in amygdala-dependent long-term synaptic plasticity and show higher basal synaptic activity at both amygdala and hippocampal synapses, showing faults in the process of memory consolidation. They also show a higher neuronal excitability, are more susceptible to convulsionant drugs and do not exhibit tolerance to chronic exposure to cannabinoids. It has also shown a protective role in the stroke-associated neuronal degeneration. With respect to non-CNS effects, Ras-GRF1 knock-out mice exhibit body weight loss, hypoinsulinemia and glucose intolerance, owing to a reduction of pancreatic beta-cells. As a regulator of the activation of Ras GTPases, Ras-GRF1 could, conceptually, participate in all the processes regulated by those, including proliferation, survival and transformation. However, its restricted expression to the brain and localization in the synaptic junctions, suggest a more specific role. By regulating the activation state of the Rac GTPases, Ras-GRF1 could participate in processes that require cytoskeletal reorganization. Thus, by coordinating the activation of Rac and H-Ras, it can control neuronal morphology and neurite outgrowth in PC12 cells, in response to NGF. Experiments in Knock-out mice also demonstrate that Ras-GRF1 controls synaptic plasticity by regulating a Rac- and p38-dependent long-term depression. Through its association with the p38 scaffolf protein IB2/JIP2, Ras-GRF1 leads to a Rac-dependant activation of the p38 cascade. Moreover, it has been demonstrated that the microtubule-destabilizing factor SCLIP can interact with Ras-GRF1, reducing its ability to activate the Rac/p38 cascade while not affecting the Ras/ERK pathway. The splice variant p75-Ras-GRF1 plays a role in the c-jun-dependent non-adherent growth in Rat1A cells. Recently, it has been shown that, in human melanoma cells, the protein Filamin-A regulates the ubiquination and destabilization of Ras-GRF1 that correlated with a decrease in the expression of MMP-9, a matrix metalloproteinase associated to different biological processes such as growth, invasion and angiogenesis.
Homology	Ras-GRF1 has a highly homologous protein: Ras-GRF2 (86% homology), which, unlike Ras-GRF1, is more ubiquitously expressed. This protein is similar in its structure to Ras-GRF1, thus also functioning as signal transducer protein. It has been also described in pancreatic beta cells, a protein of 178 aminoacids whose N terminus is identical to that of GRF1 and whose C terminus is unrelated to known proteins (GRF β).

Mutations

Note

No Ras-GRF1 mutations have been reported hitherto in human tumours. Even though overexpression of Ras-GRF1 can induce transformation of murine fibroblats and morphological changes resembling transformation processes in other cellular types, no direct associations with human malignancies have been reported thus far.

Implicated in

Entity	Cancers
Note	See above
Entity	Glucose homeostasis
Disease	Role in maintaining glucose homeostasis by regulating pancreatic beta-cells mass. Ras-GRF1 knock-out mice show a phenotype similar to manifestations of preclinical type 2 diabetes.
Entity	Neurodegenerative diseases
Disease	Role in learning and memory processes in mature neurons. Possible link to neurodegenerative diseases such as Alzheimer disease (AD) or Creutzfeldt-Jacobs disease (CJD).

External links

	Nomenclature
Hugo	RASGRF1
GDB	RASGRF1
Entrez_Gene	RASGRF1  5923  Ras protein-specific guanine nucleotide-releasing factor 1
	Cards
Atlas	RASGRF1ID43453ch15q25
GeneCards	RASGRF1
Ensembl	RASGRF1 [Search_View]   ENSG00000058335 [Gene_View]
Genatlas	RASGRF1
GeneLynx	RASGRF1
eGenome	RASGRF1
euGene	5923
	Genomic and cartography
GoldenPath	RASGRF1  -  15q25.1   chr15:77041341-77085057 -  15q24   [Description]    (hg18-Mar_2006)
Ensembl	RASGRF1 - 15q24 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	RASGRF1
	Gene and transcription
Genbank	AF370414 [ ENTREZ ]
Genbank	AK092325 [ ENTREZ ]
Genbank	AK226101 [ ENTREZ ]
Genbank	AK290135 [ ENTREZ ]
Genbank	AL359931 [ ENTREZ ]
RefSeq	NM_002891 [ SRS ]    NM_002891 [ ENTREZ ]
RefSeq	NM_153815 [ SRS ]    NM_153815 [ ENTREZ ]
RefSeq	AC_000058 [ SRS ]    AC_000058 [ ENTREZ ]
RefSeq	NC_000015 [ SRS ]    NC_000015 [ ENTREZ ]
RefSeq	NT_010194 [ SRS ]    NT_010194 [ ENTREZ ]
RefSeq	NW_925907 [ SRS ]    NW_925907 [ ENTREZ ]
AceView	RASGRF1 AceView - NCBI
Unigene	Hs.591111 [ SRS ]    Hs.591111 [ NCBI ]     HS591111 [ spliceNest ]
Fast-db	9045 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q13972 [ SRS]    Q13972 [ EXPASY ]     Q13972 [ INTERPRO ]
Prosite	PS00741 DH_1 [ SRS ]    PS00741 DH_1 [ Expasy ]
Prosite	PS50010 DH_2 [ SRS ]    PS50010 DH_2 [ Expasy ]
Prosite	PS50096 IQ [ SRS ]    PS50096 IQ [ Expasy ]
Prosite	PS50003 PH_DOMAIN [ SRS ]    PS50003 PH_DOMAIN [ Expasy ]
Prosite	PS00720 RASGEF [ SRS ]    PS00720 RASGEF [ Expasy ]
Prosite	PS50009 RASGEF_CAT [ SRS ]    PS50009 RASGEF_CAT [ Expasy ]
Prosite	PS50212 RASGEF_NTER [ SRS ]    PS50212 RASGEF_NTER [ Expasy ]
Interpro	IPR000219 DH-domain [ SRS ]    IPR000219 DH-domain [ EBI ]
Interpro	IPR001331 GDS_CDC24_CS [ SRS ]    IPR001331 GDS_CDC24_CS [ EBI ]
Interpro	IPR000048 IQ_CaM_bd_region [ SRS ]    IPR000048 IQ_CaM_bd_region [ EBI ]
Interpro	IPR001849 PH [ SRS ]    IPR001849 PH [ EBI ]
Interpro	IPR011993 PH_type [ SRS ]    IPR011993 PH_type [ EBI ]
Interpro	IPR008937 Ras_GEF [ SRS ]    IPR008937 Ras_GEF [ EBI ]
Interpro	IPR000651 RasGef_N [ SRS ]    IPR000651 RasGef_N [ EBI ]
Interpro	IPR001895 RasGRF_CDC25 [ SRS ]    IPR001895 RasGRF_CDC25 [ EBI ]
CluSTr	Q13972
Pfam	PF00612 IQ [ SRS ]    PF00612 IQ [ Sanger ]    pfam00612 [ NCBI-CDD ]
Pfam	PF00169 PH [ SRS ]    PF00169 PH [ Sanger ]    pfam00169 [ NCBI-CDD ]
Pfam	PF00617 RasGEF [ SRS ]    PF00617 RasGEF [ Sanger ]    pfam00617 [ NCBI-CDD ]
Pfam	PF00618 RasGEF_N [ SRS ]    PF00618 RasGEF_N [ Sanger ]    pfam00618 [ NCBI-CDD ]
Pfam	PF00621 RhoGEF [ SRS ]    PF00621 RhoGEF [ Sanger ]    pfam00621 [ NCBI-CDD ]
Smart	SM00015 IQ [EMBL]
Smart	SM00233 PH [EMBL]
Smart	SM00147 RasGEF [EMBL]
Smart	SM00229 RasGEFN [EMBL]
Smart	SM00325 RhoGEF [EMBL]
Blocks	Q13972
	Protein Interaction databases
DIP	Q13972
IntAct	Q13972
	Polymorphism : SNP, mutations, diseases
OMIM	606600    [ map ]
GENECLINICS	606600
SNP	RASGRF1 [dbSNP-NCBI]
SNP	NM_002891 [SNP-NCI]
SNP	NM_153815 [SNP-NCI]
SNP	RASGRF1 [GeneSNPs - Utah]  RASGRF1] [HGBASE - SRS]
HAPMAP	RASGRF1 [HAPMAP]
COSMIC	RASGRF1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	RASGRF1
	General knowledge
Family Browser	RASGRF1 [UCSC Family Browser]
SOURCE	NM_002891
SOURCE	NM_153815
SMD	Hs.591111
SAGE	Hs.591111
GO	guanyl-nucleotide exchange factor activity [Amigo]  guanyl-nucleotide exchange factor activity
GO	Rho guanyl-nucleotide exchange factor activity [Amigo]  Rho guanyl-nucleotide exchange factor activity
GO	intracellular [Amigo]  intracellular
GO	plasma membrane [Amigo]  plasma membrane
GO	long-term memory [Amigo]  long-term memory
GO	synaptosome [Amigo]  synaptosome
GO	regulation of Rho protein signal transduction [Amigo]  regulation of Rho protein signal transduction
GO	regulation of small GTPase mediated signal transduction [Amigo]  regulation of small GTPase mediated signal transduction
BIOCARTA	cdc25 and chk1 Regulatory Pathway in response to DNA damage    [Genes]
BIOCARTA	Cell Cycle: G2/M Checkpoint    [Genes]
BIOCARTA	Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle    [Genes]
BIOCARTA	RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage    [Genes]
BIOCARTA	Activation of Src by Protein-tyrosine phosphatase alpha    [Genes]
KEGG	MAPK signaling pathway
PubGene	RASGRF1
TreeFam	RASGRF1
CTD	5923 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	RASGRF1 Related clones (RZPD - Berlin)
	PubMed
PubMed	24 Pubmed reference(s) in LocusLink

Bibliography

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PMID 2181667

Isolation of multiple mouse cDNAs with coding homology to Saccharomyces cerevisiae CDC25: identification of a region related to Bcr, Vav, Dbl and CDC24.

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PMID 1396590

Cloning by functional complementation of a mouse cDNA encoding a homologue of CDC25, a Saccharomyces cerevisiae RAS activator.

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EMBO J. 1992 Jun;11(6):2151-7.

PMID 1376246

Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21.

Shou C, Farnsworth CL, Neel BG, Feig LA.

Nature. 1992 Jul 23;358(6384):351-4.

PMID 1379346

Identification of a mammalian gene structurally and functionally related to the CDC25 gene of Saccharomyces cerevisiae.

Wei W, Mosteller RD, Sanyal P, Gonzales E, McKinney D, Dasgupta C, Li P, Liu BX, Broek D.

Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7100-4.

PMID 1379731

Regulated and constitutive activity by CDC25Mm (GRF), a Ras-specific exchange factor.

Cen H, Papageorge AG, Vass WC, Zhang KE, Lowy DR.

Mol Cell Biol. 1993 Dec;13(12):7718-24.

PMID 8246988

Localization of the cellular expression pattern of cdc25NEF and ras in the juvenile rat brain.

Wei W, Schreiber SS, Baudry M, Tocco G, Broek D.

Brain Res Mol Brain Res. 1993 Sep;19(4):339-44.

PMID 8231737

Differential response of the Ras exchange factor, Ras-GRF to tyrosine kinase and G protein mediated signals.

Shou C, Wurmser A, Suen KL, Barbacid M, Feig LA, Ling K.

Oncogene. 1995 May 18;10(10):1887-93.

PMID 7761090

The N-terminal pleckstrin, coiled-coil, and IQ domains of the exchange factor Ras-GRF act cooperatively to facilitate activation by calcium.

Buchsbaum R, Telliez JB, Goonesekera S, Feig LA.

Mol Cell Biol. 1996 Sep;16(9):4888-96.

PMID 8756648

Expression of alternative forms of Ras exchange factors GRF and SOS1 in different human tissues and cell lines.

Guerrero C, Rojas JM, Chedid M, Esteban LM, Zimonjic DB, Popescu NC, Font de Mora J, Santos E.

Oncogene. 1996 Mar 7;12(5):1097-107.

PMID 8649802

Phosphorylation-dependent activation of the Ras-GRF/CDC25Mm exchange factor by muscarinic receptors and G-protein beta gamma subunits.

Mattingly RR, Macara IG.

Nature. 1996 Jul 18;382(6588):268-72.

PMID 8717044

A role for the Ras signalling pathway in synaptic transmission and long-term memory.

Brambilla R, Gnesutta N, Minichiello L, White G, Roylance AJ, Herron CE, Ramsey M, Wolfer DP, Cestari V, Rossi-Arnaud C, Grant SG, Chapman PF, Lipp HP, Sturani E, Klein R.

Nature. 1997 Nov 20;390(6657):281-6.

PMID 9384379

The Ras Guanine nucleotide Exchange Factor CDC25Mm is present at the synaptic junction.

Sturani E, Abbondio A, Branduardi P, Ferrari C, Zippel R, Martegani E, Vanoni M, Denis-Donini S.

Exp Cell Res. 1997 Aug 25;235(1):117-23.

PMID 9281359

Ras-GRF, the activator of Ras, is expressed preferentially in mature neurons of the central nervous system.

Zippel R, Gnesutta N, Matus-Leibovitch N, Mancinelli E, Saya D, Vogel Z, Sturani E.

Brain Res Mol Brain Res. 1997 Aug;48(1):140-4.

PMID 9379834

To fear or not to fear: what was the question? A potential role for Ras-GRF in memory.

Finkbeiner S, Dalva MB.

Bioessays. 1998 Sep;20(9):691-5. (Review)

PMID 9819557

Ras-GRF activates Ha-Ras, but not N-Ras or K-Ras 4B, protein in vivo.

Jones MK, Jackson JH.

J Biol Chem. 1998 Jan 16;273(3):1782-7.

PMID 9430727

Ras-specific exchange factor GRF: oligomerization through its Dbl homology domain and calcium-dependent activation of Raf.

Anborgh PH, Qian X, Papageorge AG, Vass WC, DeClue JE, Lowy DR.

Mol Cell Biol. 1999 Jul;19(7):4611-22.

PMID 10373510

G protein beta gamma subunit-dependent Rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm).

Kiyono M, Satoh T, Kaziro Y.

Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4826-31.

PMID 10220378

Activation of the Ras-GRF/CDC25Mm exchange factor by lysophosphatidic acid.

Mattingly RR, Saini V, Macara IG.

Cell Signal. 1999 Aug;11(8):603-10.

PMID 10433521

Phosphorylation of serine 916 of Ras-GRF1 contributes to the activation of exchange factor activity by muscarinic receptors.

Mattingly RR.

J Biol Chem. 1999 Dec 24;274(52):37379-84.

Signal transduction elements of TC21, an oncogenic member of the R-Ras subfamily of GTP-binding proteins.

Movilla N, Crespo P, Bustelo XR.

Oncogene. 1999 Oct 21;18(43):5860-9.

PMID 10557073

M-Ras/R-Ras3, a transforming ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6.

Quilliam LA, Castro AF, Rogers-Graham KS, Martin CB, Der CJ, Bi C.

J Biol Chem. 1999 Aug 20;274(34):23850-7.

PMID 10446149

The Rho family GTPase Cdc42 regulates the activation of Ras/MAP kinase by the exchange factor Ras-GRF.

Arozarena I, Aaronson DS, Matallanas D, Sanz V, Ajenjo N, Tenbaum SP, Teramoto H, Ighishi T, Zabala JC, Gutkind JS, Crespo P.

J Biol Chem. 2000 Aug 25;275(34):26441-8.

PMID 10840034

Induction of rac-guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) following phosphorylation by the nonreceptor tyrosine kinase Src.

Kiyono M, Kaziro Y, Satoh T.

J Biol Chem. 2000 Feb 25;275(8):5441-6.

PMID 10681520

Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3.

Ohba Y, Mochizuki N, Yamashita S, Chan AM, Schrader JW, Hattori S, Nagashima K, Matsuda M.

J Biol Chem. 2000 Jun 30;275(26):20020-6.

PMID 10777492

Maintenance of CDC42 GDP-bound state by Rho-GDI inhibits MAP kinase activation by the exchange factor Ras-GRF. evidence for Ras-GRF function being inhibited by Cdc42-GDP but unaffected by CDC42-GTP.

Arozarena I, Matallanas D, Crespo P.

J Biol Chem. 2001 Jun 15;276(24):21878-84.

PMID 11285260

Sites of phosphorylation by protein kinase A in CDC25Mm/GRF1, a guanine nucleotide exchange factor for Ras.

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J Biol Chem. 2001 Jan 19;276(3):1742-9.

PMID 11018028

Hippocampus-dependent learning and memory is impaired in mice lacking the Ras-guanine-nucleotide releasing factor 1 (Ras-GRF1).

Giese KP, Friedman E, Telliez JB, Fedorov NB, Wines M, Feig LA, Silva AJ.

Neuropharmacology. 2001 Nov;41(6):791-800.

PMID 11640934

Cloning and characterization of mouse UBPy, a deubiquitinating enzyme that interacts with the ras guanine nucleotide exchange factor CDC25(Mm)/Ras-GRF1.

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J Biol Chem. 2001 Oct 19;276(42):39448-54.

PMID 11500497

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Oncogene. 2001 Apr 19;20(17):2091-100.

PMID 11360193

Involvement of CDC25Mm/Ras-GRF1-dependent signaling in the control of neuronal excitability.

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Mol Cell Neurosci. 2001 Dec;18(6):691-701.

PMID 11749043

Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for the p38 mitogen-activated protein kinase cascade.

Buchsbaum RJ, Connolly BA, Feig LA.

Mol Cell Biol. 2002 Jun;22(12):4073-85.

PMID 12024021

Targeted disruption of Ras-Grf2 shows its dispensability for mouse growth and development.

Fernández-Medarde A, Esteban LM, Núñez A, Porteros A, Tessarollo L, Santos E.

Mol Cell Biol. 2002 Apr;22(8):2498-504.

PMID 11909944

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Prog Nucleic Acid Res Mol Biol. 2002;71:391-444. (Review)

PMID 12102558

Regulation of DNA methylation of Rasgrf1.

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Nat Genet. 2002 Jan;30(1):92-6.

PMID 11753386

Regulation of p70 S6 kinase by complex formation between the Rac guanine nucleotide exchange factor (Rac-GEF) Tiam1 and the scaffold spinophilin.

Buchsbaum RJ, Connolly BA, Feig LA.

J Biol Chem. 2003 May 23;278(21):18833-41.

PMID 12531897

Ras-GRF1 signaling is required for normal beta-cell development and glucose homeostasis.

Font de Mora J, Esteban LM, Burks DJ, Núñez A, Garcés C, García-Barrado MJ, Iglesias-Osma MC, Moratinos J, Ward JM, Santos E.

EMBO J. 2003 Jun 16;22(12):3039-49.

PMID 12805218

Activation of H-Ras in the endoplasmic reticulum by the RasGRF family guanine nucleotide exchange factors.

Arozarena I, Matallanas D, Berciano MT, Sanz-Moreno V, Calvo F, Muñoz MT, Egea G, Lafarga M, Crespo P.

Mol Cell Biol. 2004 Feb;24(4):1516-30.

PMID 14749369

Modulation of extracellular signal-regulated kinases cascade by chronic delta 9-tetrahydrocannabinol treatment.

Rubino T, Forlani G, Viganò D, Zippel R, Parolaro D.

Mol Cell Neurosci. 2004 Mar;25(3):355-62.

PMID 15033164

Developmentally regulated role for Ras-GRFs in coupling NMDA glutamate receptors to Ras, Erk and CREB.

Tian X, Gotoh T, Tsuji K, Lo EH, Huang S, Feig LA.

EMBO J. 2004 Apr 7;23(7):1567-75.

PMID 15029245

p75-Ras-GRF1 is a c-Jun/AP-1 target protein: its up regulation results in increased Ras activity and is necessary for c-Jun-induced nonadherent growth of Rat1a cells.

Leaner VD, Donninger H, Ellis CA, Clark GJ, Birrer MJ.

Mol Cell Biol. 2005 Apr;25(8):3324-37.

PMID 15798216

Endogenous expression and protein kinase A-dependent phosphorylation of the guanine nucleotide exchange factor Ras-GRF1 in human embryonic kidney 293 cells.

Norum JH, Méthi T, Mattingly RR, Levy FO.

FEBS J. 2005 May;272(9):2304-16.

PMID 15853814

Neurotrophin-dependent tyrosine phosphorylation of Ras guanine-releasing factor 1 and associated neurite outgrowth is dependent on the HIKE domain of TrkA.

Robinson KN, Manto K, Buchsbaum RJ, MacDonald JI, Meakin SO.

J Biol Chem. 2005 Jan 7;280(1):225-35.

PMID 15513915

The guanine nucleotide exchange factor RasGRF1 directly binds microtubules via DHPH2-mediated interaction.

Forlani G, Baldassa S, Lavagni P, Sturani E, Zippel R.

FEBS J. 2006 May;273(10):2127-38.

PMID 16649990

Neuronal nuclear organization is controlled by cyclin-dependent kinase 5 phosphorylation of Ras Guanine nucleotide releasing factor-1.

Kesavapany S, Pareek TK, Zheng YL, Amin N, Gutkind JS, Ma W, Kulkarni AB, Grant P, Pant HC.

Neurosignals. 2006-2007;15(4):157-73.

PMID 16921254

Distinct roles for Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 in the induction of long-term potentiation and long-term depression.

Li S, Tian X, Hartley DM, Feig LA.

J Neurosci. 2006 Feb 8;26(6):1721-9.

PMID 16467520

Age-dependent participation of Ras-GRF proteins in coupling calcium-permeable AMPA glutamate receptors to Ras/Erk signaling in cortical neurons.

Tian X, Feig LA.

J Biol Chem. 2006 Mar 17;281(11):7578-82.

PMID 16407208

SCLIP, a microtubule-destabilizing factor, interacts with RasGRF1 and inhibits its ability to promote Rac activation and neurite outgrowth.

Baldassa S, Gnesutta N, Fascio U, Sturani E, Zippel R.

J Biol Chem. 2007 Jan 26;282(4):2333-45.

PMID 17135267

Laser microdissection and microarray analysis of the hippocampus of Ras-GRF1 knockout mice reveals gene expression changes affecting signal transduction pathways related to memory and learning.

Fernández-Medarde A, Porteros A, de las Rivas J, Núñez A, Fuster JJ, Santos E.

Neuroscience. 2007 Apr 25;146(1):272-85.

PMID 17321057

Filamin A-mediated down-regulation of the exchange factor Ras-GRF1 correlates with decreased matrix metalloproteinase-9 expression in human melanoma cells.

Zhu TN, He HJ, Kole S, D'Souza T, Agarwal R, Morin PJ, Bernier M.

J Biol Chem. 2007 May 18;282(20):14816-26.

PMID 17389601

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Contributor(s)

Written	03-2008	Fernando Calvo, Piero Crespo
		Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC) - IDICAN - Universidad de Cantabria, Departamento de Biología Molecular, Facultad de Medicina.Santander, 39011, Cantabria, Spain

Citation

This paper should be referenced as such :

Calvo F, Crespo P . RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1). Atlas Genet Cytogenet Oncol Haematol. March 2008 . URL : http://AtlasGeneticsOncology.org/Genes/RASGRF1ID43453ch15q25.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:26:36 2008