Protein kinase A mediates cAMP-induced tyrosine phosphorylation of the epidermal growth factor receptor
Authors: Ivan Dikic
Robert Elez
Manfred P Lutz
Bernd Kronenberger
Albrecht Piiper
Henning Cramer
Stefan Zeuzem
Werner M√ºller-Esterl
Journal: Biochemical and Biophysical Research Communications (2003)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: cAMP concentration; tyrosine phosphorylation; epidermal growth factor receptor (EGFR); extracellular signal-regulated kinases 1/2 (ERK1/2); protein kinase A (PKA)

Abstract:  An increase in the intracellular cAMP concentration induces tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) followed by activation of extracellular signal-regulated kinases 1/2 (ERK1/2). In this report we demonstrate that these effects of cAMP are mediated via activation of protein kinase A (PKA). Chemical inhibition of PKA suppressed forskolin-induced EGFR tyrosine phosphorylation and ERK1/2 activation in PC12 cells. Furthermore, forskolin failed to induce significant tyrosine phosphorylation of the EGFR and ERK1/2 activation in PKA-defective PC12 cells. Forskolin-induced EGFR tyrosine phosphorylation was also observed in A431 cells and in membranes isolated from these cells. Phosphoamino acid analysis indicated that the recombinant catalytic subunit of PKA elicited phosphorylation of the EGFR on both tyrosine and serine but not threonine residues in A431 membranes. Together, our data indicate that activation of PKA mediates the effects of cAMP on the EGFR and ERK1/2. While PKA may directly phosphorylate the EGFR on serine residues, PKA-induced tyrosine phosphorylation of the EGFR occurs by an indirect mechanism. 

Retracted: No

PubPeer comments:
 *[right]* Fig 5B.  Western blot were used to examine the... protein expression of PRRT2 in U87 and A172 cells transfected with the miR-30b inhibitor or negative control (NC) inhibitor . *[left]* Fig 4A from [Zhou et al (2016)] .  U87 and U251 cells were transfected with miR-16 mimic with or without pc-DNA3.1-Sal-like protein 4 (SALL4) plasmid. (A and B) Following transfection, the protein level of SALL4 was then examined by western blot analysis.  , 
 Figs 3B, 8B, 10B.  Transwell assay were conducted to examine cell ... invasion .  I set up a spreadsheet to include the various papers using this versatile suite of Transwell images to represent all possible combinations of cell-lines and treatments. This is the 23rd manifestation. For comparison: Fig 3 C D from [Zhang et al (2016)] .  Transwell assay were performed to examine the migratory and invasive capacities of Saos-2 and U2OS cells transfected with miR-205 mimic or miR-negative control (NC) mimic , and Fig 7C D,  Transwell assay were performed to examine cell migration and invasion of MG63 or U2OS cells transfected with miR-205 mimic, or co-transfected with miR-205 mimic and RUNX2 plasmid .  Also *[above]* Fig 4C from [Lai, Chen Li (2015)] .  a Transwell assay were performed to examine the cell proliferation of AGS cells transfected with miR-133a mimics, miR-133a inhibitor, or co-transfected with miR-133a mimics and FSCN1 plasmid. Control: AGS cells without any transfection. *[below]* Figs 3(B), 6(B) from [Shi et al (2015)] .  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with NC scramble miRNA or miR-204 mimics, respectively. Control, Saos-2 and U-2 OS cells without any transfection ...  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with Sirt1 siRNA or co-transfected with miR-204 mimics and the Sirt1 plasmid, respectively. Control, Saos-2 and U-2 OS cells without any transfection .  Figs 3C D and 7C D from [Zhou et al (2016)] .  ... transwell assay were performed to determine cell ... invasion .  Figs 2D, 4C from [Tian et al (2016)] .  , 
 #1 *[left]* Fig 4A. *[right]* Fig 5B from Li et al (2018). *[below]* Another sighting! Fig 3F of [Xu et al (2018)] .  Western blotting was used to examine the protein levels of PANX2 in (F) U251 ... cells transfected with miR-423-3p inhibitor or NC inhibitor .  , 
 Fig 6C.  Western blot were used to examine the... protein expression of PRRT2 in glioblastoma cell lines compared with normal brain tissues .  *[left]* Fig 6C from [Liu et al (2017)] .  Western blot was used to examine the protein levels of SALL4 in normal lung epithelial BEAS-2B cells and human NSCLC cell lines A549, HCC827, H1229, and SKMES-1 . *[right]* Fig 1E from [Hu et al (2016)] .  Western blot were conducted to examine the... western expression levels of LASP1 in human NSCLC cell lines and normal human lung epithelial BEAS-2B cells.  ,