GIV (Gα-interacting vesicle-associated protein; also known as Girdin), enhances Akt activation downstream of multiple growth factor– and G-protein–coupled receptors to trigger cell migration and cancer invasion. Here we demonstrate that GIV is a tyrosine phosphoprotein that directly binds to and activates phosphoinositide 3-kinase (PI3K). Upon ligand stimulation of various receptors, GIV was phosphorylated at Tyr1764 and Tyr1798 by both receptor and non-receptor tyrosine kinases. These phosphorylation events enabled direct binding of GIV to the N- and C-terminal SH2 domains of p85α, a regulatory subunit of PI3K, stabilized receptor association with PI3K, and enhanced PI3K activity at the plasma membrane to trigger cell migration. Tyrosine phosphorylation of GIV and its association with p85α increased during metastatic progression of a breast carcinoma. These results suggest a mechanism by which multiple receptors activate PI3K through tyrosine phosphorylation of GIV, thereby making the GIVPI3K interaction a potential therapeutic target within the PI3K-Akt pathway.
GIV, a guanidine exchange factor for trimeric Gi, contains a unique domain that functions like a SH2 domain. GIV's SH2-like domain binds autophosphorylated RTKs. Binding of GIV's SH2 to RTKs enables the receptors to activate trimeric Gi. Inhibition of GIV:RTK interaction abolishes GIV-dependent Akt enhancement downstream of RTKs.
We experimentally demonstrate a visible light communication (VLC) system based on a single commercially available RGB-type LED. High spectrally efficient carrierless amplitude and phase (CAP) modulation and orthogonal frequency-division multiplexing (OFDM) are adopted in the intensity-modulation and direct-detection VLC system of limited bandwidth. In order to achieve higher capacity of the uneven-frequency-response LEDbased VLC system, OFDM signals are combined with the bit-and power-loading techniques, and CAP signals of various modulation are pre-emphasized to modulate one of the RGB chips. To reach the BER of less than 10 À3 , CAP and OFDM signals demonstrate the maximum data rates of 1.32 and 1.08 Gb/s, respectively, employing the blue chip. In addition to spectrally efficient formats, the wavelength-division-multiplexing (WDM) scheme is applied to further increase the capacity. After individually optimizing RGB chips, the maximum aggregate data rates of CAP and OFDM are 3.22 and 2.93 Gb/s, respectively, in our RGB-LED-based WDM VLC system. Hence, compared with OFDM, the CAP scheme shows competitive performance and provides an alternative spectrally efficient modulation for next generation optical wireless networks.
Hearing deterioration may begin as early as 3 months after the completion of radiotherapy. Early change may be transient, but the effect of radiation on hearing tended to be chronic and progressive.
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