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Figure 2 Z disc-related mechanical sensor cross-talks with receptor-dependent signaling. Transmembrane receptors including gp130 cytokine receptors, erbB2-erbB4, and insulin-like growth factor-1 receptor (IGF1-R) activate multiple signal kinase cascades that regulate cell protective gene programs. A calcium-activated calcineurin dephosphorylates multiple cellular substrates including transcriptional regulators that regulate cardiac remodeling. Cardiomyocytes, on the other hand, have (perhaps multiple) mechanical stress sensors inside of the cells, and the titin-T-cap-muscle-specific LIM protein (MLP) complex constitutes such a sensor systems associated with Z discs (24). Akt = protein kinase B; Jak = Janus kinase; MAP = mean arterial pressure; MKK = mitogen-activated protein kinase kinase; PDK1 = phosphoinositide-dependent protein kinase 1; SR = sarcoplasmic reticulum; Stat3 = signal transducer and activator of transcription-3.
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