The lymphocyte guard-IANs: regulation of lymphocyte survival by IAN/GIMAP family proteins

Nitta, Takeshi; Takahama, Yousuke

doi:10.1016/j.it.2006.12.002

Cited by 95 publications

(131 citation statements)

References 68 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…Therefore, murine Gimap5, despite the existence of a close related functional gimap3 gene, fulfills a nonredundant role in these contexts. Some differences between the mouse and rat may exist with respect to the role of gimap5 for intrathymic maturation of T cells: short hairpin (sh)RNA-mediated knockdown of Gimap5 in DN thymocytes disturbs the subsequent development of DP T cells in fetal thymic organ culture, 9 and similar observations (decreased DP, increased DN) have been made in the Gimap5 Ϫ/Ϫ F344 rat strain. 15 In Gimap5 Ϫ/Ϫ mice, we detect only a 2-fold reduction of CD4 Ϫ CD8 ϩ CD69 LOW Qa2 HIGH cells and a corresponding increase in the respective Qa2 LOW population, indicative of a block in the very late stages of thymic maturation.…”

Section: Discussionmentioning

confidence: 85%

“…The remaining portion of gimap5 comprises a coiled-coil region and a putative carboxyterminal membrane localization signal sequence. 9 In mice and humans, but not in rats, a putative duplication and inversion of the Gimap5 gene have occurred, resulting in the presence of a nonfunctional Gimap3 pseudogene in humans and a functional Gimap3 gene in mice.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Schulteis

Chu

Dai

et al. 2008

Blood

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Schulteis

Chu

Dai

et al. 2008

Blood

View full text Add to dashboard Cite

“…Notably, GTPases of immunity-associated proteins (GIMAPs) are highly represented among down-regulated genes (Table II; GIMAPs 1 , 6, 7, and 8). Although the precise function of GIMAPs is not known, in mice they may regulate T cell survival by modulating Bcl-2 family member activity (57)(58)(59). GIMAP expression is lymphoid restricted in mice but is broader in humans (59), and their down-regulation by TREM-1 activation and LPS may point to an important role in myeloid cell survival.…”

Section: Discussionmentioning

confidence: 99%

Innate Immune Responses to TREM-1 Activation: Overlap, Divergence, and Positive and Negative Cross-Talk with Bacterial Lipopolysaccharide

Dower

Ellis²,

Saraf³

et al. 2008

The Journal of Immunology

162

155

View full text Add to dashboard Cite

TREM-1 (triggering receptor expressed on myeloid cells-1) is an orphan immunoreceptor expressed on monocytes, macrophages, and neutrophils. TREM-1 associates with and signals via the adapter protein DAP12/TYROBP, which contains an ITAM. TREM-1 activation by receptor cross-linking has been shown to be proinflammatory and to amplify some cellular responses to TLR ligands such as bacterial LPS. To investigate the cellular consequences of TREM-1 activation, we have characterized global gene expression changes in human monocytes in response to TREM-1 cross-linking in comparison to and combined with LPS. Both TREM-1 activation and LPS up-regulate chemokines, cytokines, matrix metalloproteases, and PTGS/COX2, consistent with a core inflammatory response. However, other immunomodulatory factors are selectively induced, including SPP1 and CSF1 (i.e., M-CSF) by TREM-1 activation and IL-23 and CSF3 (i.e., G-CSF) by LPS. Additionally, cross-talk between TREM-1 activation and LPS occurs on multiple levels. Although synergy in GM-CSF protein production is reflected in commensurate mRNA abundance, comparable synergy in IL-1β protein production is not. TREM-1 activation also attenuates the induction of some LPS target genes, including those that encode IL-12 cytokine family subunits. Where tested, positive TREM-1 outputs are greatly reduced by the PI3K inhibitor wortmannin, whereas this attenuation is largely PI3K independent. These experiments provide a detailed analysis of the cellular consequences of TREM-1 activation and highlight the complexity in signal integration between ITAM- and TLR-mediated signaling.

show abstract

“…1A). This sequence motif is unique to Toc and the so called Aig-like GTPases (39). Also at the dimer interface is helix ␣5 (green in Fig.…”

Section: Homodimerization and Nucleotide Recognition Of Small Toc-gtpmentioning

confidence: 95%

On the Significance of Toc-GTPase Homodimers

Koenig

Oreb²,

Rippe

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Precursor protein translocation across the outer chloroplast membrane depends on the action of the Toc complex, containing GTPases as recognizing receptor components. The G domains of the GTPases are known to dimerize. In the dimeric conformation an arginine contacts the phosphate moieties of bound nucleotide in trans. Kinetic studies suggested that the arginine in itself does not act as an arginine finger of a reciprocal GTPase-activating protein (GAP). Here we investigate the specific function of the residue in two GTPase homologues. Arginine to alanine replacement variants have significantly reduced affinities for dimerization compared with wild-type GTPases. The amino acid exchange does not impact on the overall fold and nucleotide binding, as seen in the monomeric x-ray crystallographic structure of the Arabidopsis Toc33 arginine-alanine replacement variant at 2.0 Å . We probed the catalytic center with the transition state analogue GDP/AlF x using NMR and analytical ultracentrifugation. AlF x binding depends on the arginine, suggesting the residue can play a role in catalysis despite the non-GAP nature of the homodimer. Two non-exclusive functional models are discussed: 1) the coGAP hypothesis, in which an additional factor activates the GTPase in homodimeric form; and 2) the switch hypothesis, in which a protein, presumably the large Toc159 GTPase, exchanges with one of the homodimeric subunits, leading to activation.

show abstract

The lymphocyte guard-IANs: regulation of lymphocyte survival by IAN/GIMAP family proteins

Cited by 95 publications

References 68 publications

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Innate Immune Responses to TREM-1 Activation: Overlap, Divergence, and Positive and Negative Cross-Talk with Bacterial Lipopolysaccharide

On the Significance of Toc-GTPase Homodimers

Contact Info

Product

Resources

About