GH signaling begins with activation of the GH receptor (GHR)-associated cytoplasmic tyrosine kinase, Janus kinase-2. GH-induced Janus kinase-2 activation leads to engagement of several signaling pathways, including the extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase, phosphoinositol 3-kinase, and signal transducer and activator of transcription-5 (STAT5) pathways. ...

Although vascular endothelial growth factor (VEGFA-165) is primarily known for its role in angiogenesis, it also plays important neurotrophic and neuroprotective roles for spinal motor neurons. VEGFA-165 signals by activating its receptor tyrosine kinase VEGF receptor-2 (VEGFR-2). Because another growth/trophic factor that signals via a receptor tyrosine kinase (brain derived neurotrophic facto...

Brain-derived neurotrophic factor (BDNF) plays a key role in the differentiation and neuritogenesis of developing neurons, and in the synaptic plasticity of mature neurons, in the mammalian nervous system. BDNF binds to the receptor tyrosine kinase TrkB and transmits neurotrophic signals by activating neuron-specific tyrosine phosphorylation pathways. However, the neurotrophic function of BDNF ...

Recently, both clinical and animal studies demonstrated neuronal and glial plasticity to be important for the therapeutic action of antidepressants. Antidepressants increase glial cell line-derived neurotrophic factor (GDNF) production through monoamine-independent protein-tyrosine kinase, extracellular signal-regulated kinase (ERK), and cAMP responsive element-binding protein (CREB) activation...

The neurotrophin brain-derived neurotrophic factor (BDNF) is a potent regulator of inhibitory synaptic transmission, although the locus of this effect and the underlying mechanisms are controversial. We explored a potential interaction between BDNF and endogenous cannabinoid (endocannabinoid) signaling because activation of type 1 cannabinoid (CB1) receptors potently regulates γ-aminobutyric ac...

A limited number of whole-cell assays allow monitoring of receptor tyrosine kinase (RTK) activity in a signaling pathway-specific manner. We present the general use of the bioluminescence resonance energy transfer (BRET) technology to quantitatively study the pharmacology and signaling properties of the receptor tyrosine kinase (RTK) superfamily. RTK BRET-2 assays monitor, in living cells, the ...

Signaling by brain-derived neurotrophic factor (BDNF) via the TrkB receptor, or by neurotrophin-3 (NT3) through the TrkC receptor support distinct populations of sensory neurons. The intracellular signaling pathways activated by Trk (tyrosine kinase) receptors, which in vivo promote neuronal survival and target innervation, are not well understood. Using mice with TrkB or TrkC receptors lacking...

The WD repeat-containing protein receptor for activated protein kinase C (RACK)-1 has been linked to a variety of signaling systems including protein kinase C, growth factors, and IFNs. In the IFN system, RACK-1 functions as an adaptor recruiting the transcription factor STAT1 to the receptor complex. However, RACK-1 should play a broader role in type I IFN signaling because mutation of the RAC...

Abstract Thromboinflammation is the major cause of morbidity and mortality in COVID-19 patients, post-mortem examination demonstrates presence platelet-rich thrombi microangiopathy lung other visceral organs. Moreover, persistent microclots were detected both acute long COVID plasma samples. However, molecular mechanism SARS-CoV-2-induced thromboinflammation still unclear. We found that spleen ...