Disease relevance of Terf2ip

• Studies using Clostridium sordelii lethal toxin and Clostridium difficile toxin B have suggested that Rap-1 or Ras might transduce cAMP action [1].
• The localization of the Rap1A and B proteins transiently overexpressed with the vaccinia T7 system was identical to that observed for endogenous Rap1 proteins [2].

High impact information on Terf2ip

• Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking [3].
• This phosphorylation was required for cAMP's activation of Src and Rap1, as well as cAMP's inhibition of ERKs and cell proliferation [4].
• PKA phosphorylation of Src mediates cAMP's inhibition of cell growth via Rap1 [4].
• Src was required for cAMP activation of Rap1 and the inhibition of ERKs and cell growth [4].
• Our data identify an unsuspected connection between two families of small GTPases and imply that Rac can function downstream of cAMP/Epac1/Rap1 in a novel signal transduction secretory pathway [5].

Biological context of Terf2ip

• These results suggested that antigenic activation of naïve T cells in SPA-1-/- mice was followed by anergic rather than memory state due to the defective down-regulation of Rap1 activation, resulting in the age-dependent progression of overall T cell immunodeficiency [6].
• In addition, Rap1 was activated during cell adhesion to coated and uncoated tissue culture plates, as well as in response to various mitogens [7].
• Although Rap1 and Ras share approximately 50% overall amino acid sequence identity, the effector domains of the two proteins are identical, suggesting either similar or antagonistic signaling roles [8].
• In conclusion, interfering with Rap1 function during spermiogenesis leads to reduced fertility by impairment of germ-Sertoli cell contacts; our transgenic mouse provides an in vivo model to study the regulation of ES dynamics [9].
• Activity of Rap1 is regulated by bombesin, cell adhesion, and cell density in NIH3T3 fibroblasts [7].

Anatomical context of Terf2ip

• These results indicate that Rap1 couples cAMP signaling to a selective membrane-associated pool of p42/44MAPK to control excitability of pyramidal cells, the early and late phases of LTP, and the storage of spatial memory [10].
• To investigate the role of Rap1 as a potential signaling molecule coupling cAMP and p42/44MAPK, we expressed an interfering Rap1 mutant (iRap1) in the mouse forebrain [10].
• We show that Ras, but not Rap-1, is activated cell-specifically and mediates the cAMP-dependent activation of ERKs, while Rap-1 is not involved in this process in melanocytes [1].
• Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow [11].
• T cells from younger SPA-1-/- mice showed much greater and more persisted Rap1 activation by anti-CD3 stimulation than control T cells [6].

Associations of Terf2ip with chemical compounds

• Here, we demonstrate that Rap1 plays a pivotal role in chemokine-induced integrin activation and migration [11].
• G(alpha)(i)-dependent activation of Rap1 in platelets does not appear to be mediated by enhanced intracellular calcium release because no increase in intracellular calcium concentration was detected in response to epinephrine and because the calcium response to ADP was not diminished in platelets from the G(alpha)(i2)-/- mouse [12].
• The carboxyl-terminal guanine nucleotide exchange factor domain of AND-34, as well as the activity of its putative target Rap1, contribute to these events [13].
• We report that Reelin stimulates tyrosine phosphorylation of C3G and activates Rap1 [14].
• The guanosine trisphosphatase Rap1 serves as a critical player in signal transduction, somatic cell proliferation and differentiation, and cell-cell adhesion by acting through distinct mechanisms [9].

Regulatory relationships of Terf2ip

• Expression of Rap 1 suppresses genomic instability of H-ras transformed mouse fibroblasts [15].

Analytical, diagnostic and therapeutic context of Terf2ip

• Immunoprecipitation of Epac1 in forskolin-stimulated cells co-immunoprecipitated Rap1, p-Akt(Thr-308), and p-Akt(Ser-473) [16].
• Here, we determine the affinity of these two domains to the active forms of Ras and Rap1 using isothermal calorimetric titration [17].
• Spermatid-enriched cell cultures stimulated with 8-(4-chlorophenylthio)-cyclic AMP yielded higher levels of GTP-bound Rap1 than unstimulated cells [18].
• Furthermore fluorescent-in-situ hybridization (FISH) with a pancentromeric mouse probe showed that elevated levels of chromosome aberrations in cells expressing H-ras were also suppressed after co-expression of Rap 1 [15].

References