September 2022 GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization Overall, phagocytosis, CME, GPCR, ERK signaling, and S2R/TMEM97 are involved in the internalization of

September 2022 Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer demonstrate that exposure to SFK inhibitors, including dasatinib or knockdown of YES and Src induces ERK Dasatinib-induced ERK activation was completely abolished by exposure to the FDA-approved MEK inhibitor

Dendrite Density, Upregulated PSD95 Expression, and Abnormal Activation of the PI3K/AKT/GSK-3β and MEK/ERK Finally, we found that PI3K/AKT/GSK-3β and MEK/ERK in amygdalae of Adgra1-deficient male mice were aberrantly suppressive role of ADGRA1 in anxiety control and synaptic function by regulating the PI3K/AKT/GSK-3β and MEK/ERK

Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4 WHIM syndrome is a rare immunodeficiency disorder that is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. While several gain-of-function mutations that lead to C-terminal truncations, frame shifts and point mutations in the chemokine receptor CXCR4 have been identified in WHIM syndrome patients, the functional effect of these mutations are not fully understood. Here, we report on a new WHIM syndrome mutation that results in a frame shift within the codon for Ser339 (S339fs5) and compare the properties of S339fs5 with wild type CXCR4 and a previously identified WHIM syndrome mutant, R334X. The S339fs5 and R334X mutants exhibited significantly increased signaling compared to wild type CXCR4 including agonist-promoted calcium flux and extracellular signal-regulated kinase activation. This increase is at least partially due to a significant decrease in agonist-promoted phosphorylation, β-arrestin binding, and endocytosis of S339fs5 and R334X compared to wild type CXCR4. Interestingly, there were also significant differences in receptor degradation, with S339fs5 having a very high basal level of degradation compared to that of R334X and wild type CXCR4. In contrast to wild type CXCR4, both R334X and S339fs5 were largely insensitive to CXCL12-promoted degradation. Moreover, while basal and agonist-promoted degradation of wild type CXCR4 was effectively inhibited by the CXCR4 antagonist TE-14016, this had no effect on the degradation of the WHIM mutants. Taken together, these studies identify a new WHIM syndrome mutant, CXCR4-S339fs5, that promotes enhanced signaling, reduced phosphorylation, β-arrestin binding and endocytosis, and a very high basal rate of degradation that is not protected by antagonist treatment. Read full article

The 1994 Nobel Prize in Physiology or Medicine was awarded to Alfred Goodman Gilman and Martin Rodbell employed in GPCRs mediated signal transduction.[47] The 2000 Nobel Prize in Physiology or Medicine went to Eric Martin Rodbell – Facts - NobelPrize.org. https://www.nobelprize.org/prizes/medicine/1994/rodbell/facts Martin Rodbell – Nobel Lecture - NobelPrize.org. https://www.nobelprize.org/prizes/medicine/1994/rodbell Eric R.

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