Disease relevance of Rap1b

• In vivo, Rap1b-null mice are protected from arterial thrombosis [1].

High impact information on Rap1b

• Rap1b, an abundant small GTPase in platelets, becomes rapidly activated upon stimulation with agonists [1].
• Rap1b is required for normal platelet function and hemostasis in mice [1].
• On the other hand, retroviral expression of CalDAG-GEFI, a Rap1 exchange factor identified by megakaryocyte gene profiling as a candidate integrin regulator, enhanced agonist-induced activation of Rap1b and fibrinogen binding to alphaIIbbeta3 (P < 0.01) [2].
• cAMP-dependent oncogenic action of Rap1b in the thyroid gland [3].
• cAMP signaling leads to activation and phosphorylation of Rap1b [3].

Biological context of Rap1b

• The degree of up-regulation of Rap1b mRNA expression was proportional to the blood glucose levels [4].
• RESULTS: Rap1b cDNA had an open reading frame of 552 bp with a predicted putative protein size of approximately 21 kD [4].
• By utilizing the lambdaZAP II mouse cDNA library and SMART RACE amplification, a full-length Rap1b cDNA was isolated [4].

Anatomical context of Rap1b

• These studies establish that Rap1b can augment agonist-induced ligand binding to alpha(IIb)beta(3) through effects on integrin affinity, possibly by modulating alpha(IIb)beta(3) interactions with the actin cytoskeleton [5].

Associations of Rap1b with chemical compounds

• These data provide genetic evidence that Rap1b is involved in a common pathway of integrin activation, is required for normal hemostasis in vivo, and may be a clinically relevant antithrombotic therapy target [1].
• Cyclic AMP-dependent activation of Rap1b [6].
• The Rap1b effect was cell-autonomous and was prevented by pre-treating cells with cytochalasin D or latrunculin A to inhibit actin polymerization [5].

Analytical, diagnostic and therapeutic context of Rap1b

• Northern blot analyses revealed a single approximately 2.3 kb Rap1b mRNA transcript [4].
• In situ hybridization and immunofluorescence studies revealed that Rap1b was expressed in the inner medullary collecting tubules [4].
• Western blot analyses confirmed the hyperglycemia-induced up-regulation of the Rap1b expression [4].

References