Sam68 Is a Ras-GAP-Associated Protein in Mitosis

Guitard, Estelle; Barlat, Isabelle; Maurier, Florence; Schweighoffer, Fabien; Tocqué, Bruno

doi:10.1006/bbrc.1998.8374

Cited by 23 publications

(20 citation statements)

References 15 publications

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“…Despite the fact that Sam68 possesses a NLS, it has been found in the cytoplasm under various conditions, including poliovirus infection [27], ischemia [28], urate crystals treatment [31], HIV infection [63], sperm cell meiosis [36], mitosis [64], neuronal depolarization [32], signaling transduction [8], and in some mouse cells [15]. The findings that Sam68 can be rapidly accumulated in the cytoplasm during acute conditions such as depolarization and ischemia suggest a shuttling mechanism; however, classical heterokaryon assays have failed to detect any apparent nuclear-cytoplasmic shuttling of Sam68 [65].…”

Section: Discussionmentioning

confidence: 99%

Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1

Henao‐Mejia

2009

Experimental Cell Research

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Sam68 has been implicated in a variety of important cellular processes such as RNA metabolism and intracellular signaling. We have recently shown that Sam68 cytoplasmic mutants induces stress granules (SG) and inhibit HIV-1 nef mRNA translation [1]. These findings prompted us to investigate the possibility and the underlying mechanisms of the wild-type counterpart Sam68 SG recruitment. Herein, we revealed that Sam68 was significantly recruited into cytoplasmic SG under oxidative stress. We then demonstrated that domain aa269–321 and KH domain were both essential for this recruitment. Nevertheless, Sam68 knockdown had no effects on SG assembly, indicating that Sam68 is not a constitutive component of the SG. Moreover, we showed that Sam68 cytoplasmic mutants-induced SG formation was independent of eIF2α phosphorylation. Lastly, we demonstrated that Sam68 was complexed with T-cell intracellular antigen-1 (TIA-1), a core SG component, and that the complex formation was correlated with Sam68 SG recruitment. Taken together, these results provide direct evidence for the first time that Sam68 is recruited into SG through complexing with TIA-1 in response to oxidative stress and suggest that cytoplasmic SG recruitment of Sam68 and ensuing changes in Sam68 physiological functions are part of the host response to external stressful conditions.

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Section: Discussionmentioning

confidence: 99%

Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1

Henao‐Mejia

2009

Experimental Cell Research

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“…Moreover, it has been shown that insulin stimulation increases PI3K activity in Sam68 immunoprecipitates, suggesting that the association of tyrosine-phosphorylated Sam68 with the regulatory subunit p85 also correlates with an increase in PI3K activity. Sam68 was previously described to associate with Ras-GAP in mitosis by interacting with the SH2 domains [39,63]. Sam68 tyrosine phosphorylated by insulin receptor also associates with Ras-GAP, via the SH2 domains, recruiting this signaling protein to the PI3K pathway.…”

Section: Sam68 and Insulin Receptor Signalingmentioning

confidence: 98%

“…Tyrosine phosphorylation of Sam68 leads to its association with different SH2 domain-containing proteins [45], including kinases of the Src family [3][4][5][6][7], Sik/BRK [24], as well as the kinases of the Itk/Tec family [37,38]. Moreover, tyrosine-phosphorylated Sam68 can also interact with SH2-containing adaptor proteins and signaling enzymes such as Grb2 [4,41], Grap [41], Nck [42], PLCg-1 [4], Ras-GAP [4,46,63] and p85a-PI3K [29,39]. The association of Sam68 with these SH2 domains exhibits different affinities.…”

Section: Sam68 and Protein-protein Interactionsmentioning

confidence: 99%

Role of Sam68 as an adaptor protein in signal transduction

Najib

Martín-Romero

González-Yanes

et al. 2005

CMLS, Cell. Mol. Life Sci.

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Sam68, the substrate of Src in mitosis, belongs to the family of RNA binding proteins. Sam68 contains consensus sequences to interact with other proteins via specific domains. Thus, Sam68 has various proline-rich sequences to interact with SH3 domain-containing proteins. Moreover, Sam68 also has a C-terminal domain rich in tyrosine residues that is a substrate for tyrosine kinases. Tyrosine phosphorylation of Sam68 promotes its interaction with SH2 containing proteins. The association of Sam68 with SH3 domain-containing proteins, and its tyrosine phosphorylation may negatively regulate its RNA binding activity. The presence of these consensus sequences to interact with different domains allows this protein to participate in signal transduction pathways triggered by tyrosine kinases. Thus, Sam68 participates in the signaling of T cell receptors, leptin and insulin receptors. In these systems Sam68 is tyrosine phosphorylated and recruited to specific signaling complexes. The participation of Sam68 in signaling suggests that it may function as an adaptor molecule, working as a dock to recruit other signaling molecules. Finally, the connection between this role of Sam68 in protein-protein interaction with RNA binding activity may connect signal transduction of tyrosine kinases with the regulation of RNA metabolism.

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“…Studies in T-cells indicate that Sam68 may function as an adaptor linking the TCRcoupled Src family kinases Fyn and Lck to downstream e ectors (Vogel and Fujita, 1995;Fusaki et al, 1997;Lang et al, 1999). Numerous other partnerships with di erent SH2 and SH3 domain-containing signaling molecules have also been documented including: PLCg-1, Grb2, Nck, Jak3, SHP-1, Cbl, Grap (Grb2-like protein), the p21 ras GTPase activating protein, the p85 subunit of PI3-kinase, p47 phox and Tec kinase family Finan et al, 1996;Bunnell et al, 1996;Fusaki et al, 1997;Guinamard et al, 1997;Jabado et al, 1997Jabado et al, , 1998Lawe et al, 1997;Trub et al, 1997;Guitard et al, 1998).…”

Section: Nuclear and Perinuclear Targets Of Srcmentioning

confidence: 99%

Selected glimpses into the activation and function of Src kinase

2000

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Since the discovery of the v-src and c-src genes and their products, much progress has been made in the elucidation of the structure, regulation, localization, and function of the Src protein. Src is a non-receptor protein tyrosine kinase that transduces signals that are involved in the control of a variety of cellular processes such as proliferation, di erentiation, motility, and adhesion. Src is normally maintained in an inactive state, but can be activated transiently during cellular events such as mitosis, or constitutively by abnormal events such as mutation (i.e. v-Src and some human cancers). Activation of Src occurs as a result of disruption of the negative regulatory processes that normally suppress Src activity, and understanding the various mechanisms behind Src activation has been a target of intense study. Src associates with cellular membranes, in particular the plasma membrane, and endosomal membranes. Studies indicate that the di erent subcellular localizations of Src could be important for the regulation of speci®c cellular processes such as mitogenesis, cytoskeletal organization, and/or membrane tra cking. This review will discuss the history behind the discovery and initial characterization of Src and the regulatory mechanisms of Src activation, in particular, regulation by modi®cation of the carboxyterminal regulatory tyrosine by phosphatases and kinases. Its focus will then turn to the di erent subcellular localizations of Src and the possible roles of nuclear and perinuclear targets of Src. Finally, a brief section will review some of our present knowledge regarding Src involvement in human cancers. Oncogene (2000) 19, 5620 ± 5635.

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Sam68 Is a Ras-GAP-Associated Protein in Mitosis

Cited by 23 publications

References 15 publications

Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1

Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1

Role of Sam68 as an adaptor protein in signal transduction

Selected glimpses into the activation and function of Src kinase

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