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JAM-A protects from thrombosis by suppressing integrin αIIbβ3-dependent outside-in signaling in platelets
| Content Provider | Scilit |
|---|---|
| Author | Naik, Meghna U. Stalker, Timothy J. Brass, Lawrence F. Naik, Ulhas P. |
| Copyright Year | 2012 |
| Description | Mounting evidence suggests that agonist-initiated signaling in platelets is closely regulated to avoid excessive responses to injury. A variety of physiologic agonists induce a cascade of signaling events termed as inside-out signaling that culminate in exposure of high-affinity binding sites on integrin $α_{IIb}β_{3}$. Once platelet activation has occurred, integrin $α_{IIb}β_{3}$ stabilizes thrombus formation by providing agonist-independent “outside-in” signals mediated in part by contractile signaling. Junctional adhesion molecule A (JAM-A), a member of the cortical thymocyte marker of the Xenopus (CTX) family, was initially identified as a receptor for a platelet stimulatory mAb. Here we show that JAM-A in resting platelets functions as an endogenous inhibitor of platelet function. Genetic ablation of Jam-A in mice enhances thrombotic function of platelets in vivo. The absence of Jam-A results in increase in platelet aggregation ex vivo. This gain of function is not because of enhanced inside-out signaling because granular secretion, Thromboxane A2 (TxA2) generation, as well as fibrinogen receptor activation, are normal in the absence of Jam-A. Interestingly, integrin outside-in signaling such as platelet spreading and clot retraction is augmented in Jam-A–deficient platelets. We conclude that JAM-A normally limits platelet accumulation by inhibiting integrin outside-in signaling thus preventing premature platelet activation. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321861/pdf |
| Ending Page | 3360 |
| Page Count | 9 |
| Starting Page | 3352 |
| DOI | 10.1182/blood-2011-12-397398 |
| Journal | Blood |
| Issue Number | 14 |
| Volume Number | 119 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2012-04-05 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Integrin Jam Signaling in Platelets Agonist Sub Function of Platelets Activation Journal: Blood (Vol- 124, Issue- 14) |
| Content Type | Text |
| Resource Type | Article |
