Catalytic activity of the mouse guanine nucleotide exchanger mSOS is activated by Fyn tyrosine protein kinase and the T-cell antigen receptor in T cells.

Li, Bao-Qun; Subleski, Marianne; Fusaki, Noemi; Yamamoto, Tadashi; Copeland, Terry D.; Princler, Gerald L.; Kung, Hsiang‐Fu; Kamata, Tohru

doi:10.1073/pnas.93.3.1001

Cited by 46 publications

(37 citation statements)

References 32 publications

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“…In support of this idea, constitutive or conditional membrane targeting of these exchange factors has been shown to strengthen Ras activation in transfected cells (11,12). However, some reports suggest that regardless of sub-cellular location, the intrinsic Ras guanine nucleotide exchange activity of Sos (Ras-GEF activity) may differ before and after stimulation of surface tyrosine kinase receptors (13,14).…”

mentioning

confidence: 92%

hSos1 Contains a New Amino-terminal Regulatory Motif with Specific Binding Affinity for Its Pleckstrin Homology Domain

Jorge

Zarich

Oliva

et al. 2002

Journal of Biological Chemistry

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The protein hSos1 is a Ras guanine nucleotide exchange factor. In the present study, we investigated the function of the amino-terminal region of the hSos1 protein, corresponding to the first 600 residues, which includes the Dbl and pleckstrin homology (DH and PH) domains. We demonstrated, using a series of truncated mutants, that this region is absolutely necessary for hSos1 activity. Our results suggest that the first 200 residues (upstream of DH domain), which we called the HF motif on the basis of their homology with histone H2A, may exert negative control over the functional activity of the whole hSos1 protein. In vitro binding analysis showed that the HF motif is able to interact specifically with the PH domain of hSos1. The amino-terminal region of hSos1 may be associated in vivo with an expressed HF motif. These findings document the existence of the HF motif located upstream of the DH domain in the hSos1 protein. This motif may be responsible for the negative control of hSos1, probably by intramolecular binding with the PH domain.

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mentioning

confidence: 92%

hSos1 Contains a New Amino-terminal Regulatory Motif with Specific Binding Affinity for Its Pleckstrin Homology Domain

Jorge

Zarich

Oliva

et al. 2002

Journal of Biological Chemistry

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“…For both B-cell and T-cell antigen receptors, Ras activation seems to be at least partially dependent on tyrosine kinases, and the stimulation of these receptors can lead to the formation of complexes of Shc, Grb2, and/or Sos (31,39,58,60), suggesting that Ras activation can occur through a mechanism similar to the relatively well-characterized recruitment of Sos to receptor tyrosine kinases such as epidermal growth factor receptor. However, Sos has not yet been detected in antigen receptor complexes (8,49).…”

Section: Discussionmentioning

confidence: 99%

“…All lymphocytes probably express Sos, and this GEF has been implicated in Ras activation occurring downstream of T-cell and B-cell receptors (31,39,58,60). However, in at least some circumstances, T-cell receptor signalling that leads to Ras activation does not seem to result in recruitment of Sos to receptor complexes (8,49).…”

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confidence: 99%

Regulation of RasGRP via a Phorbol Ester-Responsive C1 Domain

Tognon

Kirk

Passmore

et al. 1998

Molecular and Cellular Biology

219

207

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As part of a cDNA library screen for clones that induce transformation of NIH 3T3 fibroblasts, we have isolated a cDNA encoding the murine homolog of the guanine nucleotide exchange factor RasGRP. A point mutation predicted to prevent interaction with Ras abolished the ability of murine RasGRP (mRasGRP) to transform fibroblasts and to activate mitogen-activated protein kinases (MAP kinases). MAP kinase activation via mRasGRP was enhanced by coexpression of H-, K-, and N-Ras and was partially suppressed by coexpression of dominant negative forms of H-and K-Ras. The C terminus of mRasGRP contains a pair of EF hands and a C1 domain which is very similar to the phorbol ester-and diacylglycerol-binding C1 domains of protein kinase Cs. The EF hands could be deleted without affecting the ability of mRasGRP to transform NIH 3T3 cells. In contrast, deletion of the C1 domain or an adjacent cluster of basic amino acids eliminated the transforming activity of mRasGRP. Transformation and MAP kinase activation via mRasGRP were restored if the deleted C1 domain was replaced either by a membrane-localizing prenylation signal or by a diacylglycerol-and phorbol ester-binding C1 domain of protein kinase C. The transforming activity of mRasGRP could be regulated by phorbol ester when serum concentrations were low, and this effect of phorbol ester was dependent on the C1 domain of mRasGRP. The C1 domain could also confer phorbol myristate acetate-regulated transforming activity on a prenylation-defective mutant of K-Ras. The C1 domain mediated the translocation of mRasGRP to cell membranes in response to either phorbol ester or serum stimulation. These results suggest that the primary mechanism of activation of mRasGRP in fibroblasts is through its recruitment to diacylglycerolenriched membranes. mRasGRP is expressed in lymphoid tissues and the brain, as well as in some lymphoid cell lines. In these cells, RasGRP has the potential to serve as a direct link between receptors which stimulate diacylglycerol-generating phospholipase Cs and the activation of Ras.

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“…Fyn is also activated rapidly after ligandinduced PRLr dimerization. As shown by this laboratory and others (Clevenger & Medaglia 1994, Li et al 1996, direct substrates for PRL-activated Fyn include the guanine-nucleotide exchange factors Sos and Vav, which serve to activate both Ras and Rac G-proteins. Acting as allosteric activators, both Ras and Rac serve to activate kinase cascades that ultimately activate the dual specificity kinase MAPK and S6 kinase that can directly phosphorylate and activate numerous transcription factors, such as Jun, Fos, p62, etc.…”

Section: Proximal Signaling-protein Tyrosine Kinasesmentioning

confidence: 99%