Transregulation of the epidermal growth factor receptor (EGFR) by protein kinase C (PKC) serves as a model for heterologous desensitization of receptor tyrosine kinases, but the underlying mechanism remained unknown. By using c-Cbl-induced ubiquitination of EGFR as a marker for transfer from early to late endosomes, we provide evidence that PKC can inhibit this process. In parallel, receptor down-regulation and degradation are significantly reduced. The inhibitory effects of PKC are mediated by a single threonine residue (threonine 654) of EGFR, which serves as a major PKC phosphorylation site. Biochemical and morphological analyses indicate that threonine-phosphorylated EGFR molecules undergo normal internalization, but instead of sorting to lysosomal degradation, they recycle back to the cell surface. In conclusion, by sorting EGFR to the recycling endosome, heterologous desensitization restrains ligand-induced down-regulation of EGFR.

No abstract

cancer ͉ oncogene ͉ signal transduction ͉ tyrosine kinase ͉ ubiquitin

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been discovered as the pathogenic cause of the coronavirus disease 19 (COVID-19). Cellular entry of SARS-CoV-2 are mediated by the spike glycoprotein of virus, and the host specific receptors and proteases. Recently, besides pulmonary complications as the chief symptom, investigations have also revealed that SARS-CoV-2 can trigger neurological manifestations. Herein, to investigate the expression level of receptors and related proteases is important for understanding the neuropathy in COVID-19. We determined the expression levels of receptor ACE2 and CD147, and serine protease TMPRSS2 in human and mouse brain cell lines and mouse different region of brain tissues with qRT-PCR and Western blot. The results showed that the expression pattern of all them was very different to that of lung. ACE2 is lower but CD147 is higher expressed in mostly brain cell lines and mouse brain tissues comparing with lung cell line and tissue, and TMPRSS2 has consistent expression in brain cell lines and mouse lung tissues. It is suggested that SARS-CoV-2 might have a different way of infection to cerebral nervous system. Our finding will offer the clues to predict the possibility of SARS-CoV-2 infection to human brain nervous system and pathogenicity.

No abstract