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These proteins have a key role in coordinating multiple extracellular signaling pathways during embryonic development of chicken, frog and mouse [ 85].
Differentiation into osteoclasts is dependent on multiple extracellular signaling molecules, including macrophage colony-stimulating factor (MCSF), receptor activator for nuclear factor κB ligand (RANKL), tumor necrosis factor, interferon gamma, and inter-leukins [ 41].
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This is a complex developmental process regulated by multiple extracellular signals and transduction pathways.
Actin cytoskeleton appears to be the master regulator of the Hippo-YAP/TAZ pathway, and multiple extracellular signals are integrated to the cytoskeleton reorganization to transduce the signals to the core of the Hippo kinases module.
The mitogen-activated protein kinases (MAPK) are involved in the integration and processing of multiple extracellular signals and their induction triggers diverse biological responses (reviewed in [8], [9]).
Meanwhile, multiple extracellular signals including TGF- β, Notch1, EGF, and hypoxia can initiate the EMT process.
Thus, integration of multiple extracellular signals are needed to activate the angiogenic switch.
These findings provide critical insights into the control of chondrocytes through the integration of multiple extracellular signals.
Indeed, autocrine signaling has been shown to be part of a positive feedback system that integrates multiple extracellular signals into a single output [ 9].
Multiple extracellular signals including TGF-β, receptor tyrosine kinases, Notch, nuclear factor kappa B (NFκB), and Wnt can initiate the type 3 EMT program.
The inositol 1,4,5-trisphosphate receptor (InsP3R) is an intracellular calcium release channel that can be activated by multiple extracellular signals, including hormones and neurotransmitters.
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