Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton

Matsumoto, Ken; Asano, Takuya; Endo, Takeshi

doi:10.1038/sj.onc.1201416

Cited by 83 publications

(93 citation statements)

References 33 publications

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“…This intriguing expression pattern is similar to that of a recently identified Ras-related GTPase, R-Ras3/M-Ras, of which the transcript is also abundant in brain and heart (24,25). R-Ras3/M-Ras has been shown to have transforming activity in NIH 3T3 cells (26,27), but Di-Ras lacked the activity in the cells (data not shown).…”

Section: Failure Of Di-ras To Stimulate Mitogen-activated Protein Kinmentioning

confidence: 52%

Di-Ras, a Distinct Subgroup of Ras Family GTPases with Unique Biochemical Properties

Kontani¹,

Tada²,

Ogawa³

et al. 2002

Journal of Biological Chemistry

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The small GTPase Ras family regulates a variety of cell functions including proliferation and differentiation. Here we have identified novel Ras members, human Di-Ras1 and Di-Ras2, belonging to a distinct branch of the GTPase family. Di-Ras1 and Di-Ras2 specifically expressed in heart and brain share 30 -40% overall identity with other members of Ras family, however, they have the following characteristic substitutions at highly conserved regions among the Ras family. 1) Thr-63 and Ser-65 in Di-Ras are substituted for Ala-59 and Gln-61 positions in Ha-Ras, respectively, that are known to be critical for GTP hydrolysis. 2) Within the effector domains, Di-Ras has Ile at a position corresponding to Asp-33 in Ha-Ras, which is important for its interaction with the downstream effector Raf. As predicted by these substitutions, Di-Ras has only a quite low level of GTPase activity and exists predominantly as a GTPbound form upon its expression in living cells. Moreover, Di-Ras fails to interact with the Ras-binding domain of Raf, resulting in no stimulation of mitogenactivated protein kinase. Interestingly, introduction of Di-Ras into HEK293T cells induces large cellular vacuolation. These findings raise the possibility that Di-Ras might regulate cell morphogenesis in a manner distinct from other members of Ras family.The small GTPase Ras family acts as a molecular switch that regulates a wide range of cell functions including proliferation and differentiation (1-3). Ras is activated in response to a variety of extracellular signals, resulting in stimulation of tyrosine kinases either directly or indirectly. The small GTPase, which cycles between active GTP-bound and inactive GDPbound states, is activated by guanine nucleotide exchange factors that enhance the exchange of bound GDP for GTP and is deactivated by GTPase-activating proteins that increase the intrinsic rate of hydrolysis of bound GTP. The GTP-bound form of Ras associates with several effector molecules, most notably members of the Raf family, the RalGDS family and phosphoinositide 3-kinase. Amino acid residues 32-40 of Ras are important for its interaction with effector molecules and designated as the "effector domain" (4). The biological consequences of their interactions depend greatly on the cell type and on the context of other signaling events.The members of Ras family, at least 13 at present, are characterized by extensive similarities in their effector domains (5). Besides three Ras proteins (Ha-Ras, Ki-Ras, and N-Ras), there are four Rap proteins (Rap1A, Rap1B, Rap2A, and Rap2B), two Ral proteins (RalA and RalB), R-Ras, TC21, R-Ras3/M-Ras, and Rheb in the Ras family. Although many Ras members can interact with the same effector molecules as the three Ras proteins, the physiological roles of most Ras-like GTPases are not fully understood.More recently, some members of the Ras family have begun to be analyzed. For example, Rap1, the closest relative of Ras, has attracted much attention because of the possibility that it functions independently or coor...

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Section: Failure Of Di-ras To Stimulate Mitogen-activated Protein Kinmentioning

confidence: 52%

Di-Ras, a Distinct Subgroup of Ras Family GTPases with Unique Biochemical Properties

Kontani¹,

Tada²,

Ogawa³

et al. 2002

Journal of Biological Chemistry

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“…TC21 is also considered as a member of the R-Ras gene subfamily. The other two members in this subfamily include R-Ras (also known as R-Ras1, Lowe and Goeddel, 1987) and R-Ras3 (also known as M-Ras, Kimmelman et al, 1997;Matsumoto et al, 1997). All members of R-Ras subfamily show a high degree of sequence identity to the Ras proteins, particularly in N-terminal catalytic domain of these proteins (reviewed in Bos, 1997).…”

Section: Introductionmentioning

confidence: 99%

TC21 mediates transformation and cell survival via activation of phosphatidylinositol 3-kinase/Akt and NF-κB signaling pathway

Rong

Liu

et al. 2002

Oncogene

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“…In addition, several of the subfamily members have been shown to be oncogenically activated in human tumors as well as possess transforming ability in cultured cells. These include H-, K-, and N-ras (Bos, 1989), R-Ras (Saez et al, 1994;Cox et al, 1994), TC21 (Graham et al, 1994;Huang et al, 1995) and most recently RRas3, also referred to as M-Ras (Kimmelman et al, 1997;Matsumoto et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

R-Ras3, a brain-specific Ras-related protein, activates Akt and promotes cell survival in PC12 cells

2000

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Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton

Cited by 83 publications

References 33 publications

Di-Ras, a Distinct Subgroup of Ras Family GTPases with Unique Biochemical Properties

Di-Ras, a Distinct Subgroup of Ras Family GTPases with Unique Biochemical Properties

TC21 mediates transformation and cell survival via activation of phosphatidylinositol 3-kinase/Akt and NF-κB signaling pathway

R-Ras3, a brain-specific Ras-related protein, activates Akt and promotes cell survival in PC12 cells

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