2015
DOI: 10.1172/jci77993
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RASA3 is a critical inhibitor of RAP1-dependent platelet activation

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Cited by 119 publications
(159 citation statements)
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References 75 publications
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“…25 Once a IIb b 3 has been activated, integrin-dependent signaling promotes clot retraction, increasing packing density and slowing solute transport.…”
Section: The Platelet Signaling Network Is An Integrating Enginementioning
confidence: 99%
See 1 more Smart Citation
“…25 Once a IIb b 3 has been activated, integrin-dependent signaling promotes clot retraction, increasing packing density and slowing solute transport.…”
Section: The Platelet Signaling Network Is An Integrating Enginementioning
confidence: 99%
“…[26][27][28] For Rap1b, the primary GAP is Rasa3. 25,29 Network integration occurs in part by regulating the balance of GEF and GAP activity. The availability of RGS10 and RGS18 is regulated by spinophilin (SPL), which sequesters both in resting platelets, and by 14-3-3g, which binds RGS proteins in activated platelets.…”
Section: The Platelet Signaling Network Is An Integrating Enginementioning
confidence: 99%
“…The active GTP‐bound Gαi‐subunit dissociates from the β and γ subunits and binds to AC leading to diminished cAMP synthesis (Figure 3 and Table 1). Simultaneously Gi triggers the phosphatidylinositol 3‐kinase (PI3K) pathway, which converts phosphatidylinositol 4,5‐bisphosphate to phosphatidylinositol 3,4,5‐trisphosphate at the plasma membrane leading to the activation of the kinase Akt and inhibition of the Rap1‐GAP RASA3, key activating pathways in platelets 20, 21, 22. The synergism between P2Y12 function and blockage of cyclic nucleotide pathways has been shown for both, cAMP and cGMP components, although cGMP regulation by P2Y12 is not well understood 9, 23.…”
Section: Interactions At Receptor Levelmentioning
confidence: 99%
“…During platelet activation Rap1GAP2 S9 phosphorylation enhances 14‐3‐3 binding, whereas PKA/PKG‐mediated S7 phosphorylation does the opposite (Figure 7). 92 Platelet activation has also been shown to inhibit the function of RASA3, a highly expressed GAP of Rap1 in platelets, in a PI3K‐dependent manner 21, 22. Vasodilator‐stimulated phosphoprotein (VASP) is an actin filament and focal adhesion binding protein and was one of the first substrates of PKA/PKG to be identified in platelets.…”
Section: Interactions Involving Small G‐proteinsmentioning
confidence: 99%
“…For firm platelet adhesion to occur, RASA3 activity has to be down-modulated. Critical for the down-modulation of Rasa3 activity is signaling via the Gi-coupled receptor for ADP, P2Y12[61]. Thus, similar to the GPCR dual receptor systems, RAP activation is a two-step process.…”
Section: Classical Hemostasis – Balancing Platelet Adhesiveness In CImentioning
confidence: 99%