Bruton's tyrosine kinase (Btk) is required for B cell development and signal transduction through cell-surface molecules such as BCR and IL-5 receptor. We have identified a Btk-associated molecule, BAM11 (hereafter referred to as BAM) that binds to the pleckstrin homology (PH) domain of Btk, and inhibits Btk activity both in vivo and in vitro. In this study, we demonstrate BAM's transcriptional co-activation activity and its functional interaction with Btk. By using transient transcription assays, we demonstrate that the enforced expression of BAM enhances transcriptional activity of the synthetic reporter gene. The C-terminus of BAM is essential for the transcriptional co-activation activity. The ectopic expression of Btk together with BAM enhances BAM's transcriptional co-activation activity. BAM's transcriptional co-activation activity is enhanced through interaction with Btk, and requires both its intact PH domain and functional kinase activity. We also show that enforced expression of TFII-I, another Btk-binding protein with transcriptional activity, together with BAM and Btk, further augments BAM- and Btk-dependent transcriptional co-activation. Furthermore, BAM can be co-immunoprecipitated with the INI1/SNF5 protein, a member of the SWI/SNF complex that remodels chromatin and activates transcription. We propose a model in which Btk regulates gene transcription in B cells by activating BAM and the SWI/SNF transcriptional complex via TFII-I activation.

APS (adaptor molecule containing PH and SH2 domains) is an intracellular adaptor protein that forms an

No abstract

Electromyographycontrolled gamified exercise system for the distal upper extremity: a usability assessment in subacute post-stroke patients, Disability and Rehabilitation: Assistive Technology,

Neural interactions between upper and lower limbs underlie motor coordination in humans. Specifically, upper limb voluntary muscle contraction can facilitate spinal and corticospinal excitability of the lower limb muscles. However, little remains known on the involvement of somatosensory information in arm‐leg neural interactions. Here, we investigated effects of voluntary and electrically induced wrist flexion on corticospinal excitability and somatosensory information processing of the lower limbs. In Experiment 1, we measured transcranial magnetic stimulation (TMS)‐evoked motor evoked potentials (MEPs) of the resting soleus (SOL) muscle at rest or during voluntary or neuromuscular electrical stimulation (NMES)‐induced wrist flexion. The wrist flexion force was matched to 10% of the maximum voluntary contraction (MVC). We found that SOL MEPs were significantly increased during voluntary, but not NMES‐induced, wrist flexion, compared to the rest (P < .001). In Experiment 2, we examined somatosensory evoked potentials (SEPs) following tibial nerve stimulation under the same conditions. The results showed that SEPs were unchanged during both voluntary and NMES‐induced wrist flexion. In Experiment 3, we examined the modulation of SEPs during 10%, 20% and 30% MVC voluntary wrist flexion. During 30% MVC voluntary wrist flexion, P50‐N70 SEP component was significantly attenuated compared to the rest (P = .003). Our results propose that the somatosensory information generated by NMES‐induced upper limb muscle contractions may have a limited effect on corticospinal excitability and somatosensory information processing of the lower limbs. However, voluntary wrist flexion modulated corticospinal excitability and somatosensory information processing of the lower limbs via motor areas.