Effectors, downstream

The Gpy dimer appears to function as a rigid unit with critical residues positioned to interact with Ga-GDP. Whereas Ga activation proceeds through nucleotide-dependent structural reorganization, activation of Gpy occurs solely as a function of its release from Ga. As we will see, the Ga subunit acts as a negative regulator of Gpy by masking sites on the surface of Gpy that interact with downstream effector molecules. 

Kinins are a group of peptide hormones of 8-11 residues that act locally as proinflammatory agents, often through the release of powerful downstream effectors such as nitric oxide and/or prostaglandins. 

Ras is a G protein that cycle between two conformations, an activated Ras-GTP or inactivated form Ras-GDP. Ras, attached to the cell membrane by lipidation, is a key component in many signalling cascades, which couple growth factor receptors to downstream effectors that control such processes as cytoskeletal integrity, proliferation, cell adhesion, apoptosis and cell migration. Mutations and dysregulations of the Ras protein leading to increased invasion and metastasis, and decreased apoptosis are very common in cancers. 

Sorafenib is a multitargeted cancer therapy that inhibits VEGFR, PDGFR, KIT, fetal liver tyrosine kinase 3 (FLT-3), and the serine/threonine kinase RAF. RAF kinase is a key downstream effector of Ras in the MAPK/Ras signal-transduction pathway that has been linked to various cancers. Sorafenib is both a tyrosine kinase inhibitor and serine/threonine signal-transduction inhibitor. Sorafenib has been approved in renal cancer. 

Ubiquitin modification of substrates can be sensed by proteins, which serve as ubiquitin receptors. These proteins harbor domains capable of ubiquitin binding and help to translate the signal into the proper physiological response by forming signaling complexes or activating downstream effectors. So far more than 15 different ubiquitin recognition motifs have been identified. 

Studies on mixed gUal/neuronal cerebrocortical cultures from wild type mice and CXCR4-deficient mice show that HTV envelope proteins are able to cause neurotoxicity through CXCR4 or CCR5 by the activation of p38 and specific downstream effector... 

The major 3 -phosphoinositide products of class I PI3Ks are phosphati-dylinositol 3,4,5-trisphosphate [PI(3,4,5)P3, which is formed primarily from phosphorylation of PI(4,5)P2) and its metabolite phosphatidylinositol 3,4-bisphosphate, PI(3,4)P2]. The basal levels of PI(3,4)P2 and PI(3,4,5)P3 in cells are usually in low abundance but can rise sharply after cell stimulation to interact with an array of protein effectors via pleckstrin homology (PH) domains, modular segments of about 100 amino acids found in many signaling proteins. It is these PH-domain-containing proteins that are able to propagate and drive downstream signaling events. 

Dl-iike receptors activate the Gs transduction pathway, stimulating the production of adenylyl cyclase, which increases the formation of cyclic adenosine monophosphate (cAMP) and ultimately increases the activity of cAMP-dependent protein kinase (PKA). PKA activates DARPP-32 (dopamine and cyclic adenosine 3, 5 -monophosphate-regulated phosphoprotein, 32 kDa) via phosphorylation, permitting phospho-DARPP-32 to then inhibit protein phosphatase-1 (PP-1). The downstream effect of decreased PP-1 activity is an increase in the phosphorylation states of assorted downstream effector proteins regulating neurotransmitter... 

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