Erk 5 is necessary for sustained PDGF-induced Akt phosphorylation and inhibition of apoptosis.
Extracellular regulated kinase (Erk) 5 is a member of the mitogen activated protein (MAP) kinase family that has been implicated in both cell proliferation and survival. In the present study, we found that stimulation with platelet-derived growth factor (PDGF)-BB leads to a transient activation of Erk5, which was shown to be dependent on recruitment of both Src kinases and the tyrosine phosphatase Shp2 to the activated PDGF receptor beta (PDGFRbeta). We could also demonstrate that Shp2 docking to the receptor is critical for Src kinase activation, suggesting that Shp2 may contribute to Erk5 activation through its involvement in Src kinase activation. Under control conditions, PDGF-BB promoted a sustained Akt phosphorylation. However, reduction of the expression of Erk5 by siRNA resulted in only a transient Akt phosphorylation, and an inability of PDGF-BB to suppress caspase 3 activation and inhibit apoptotic nuclear morphological changes such as condensed or fragmented chromatin under serum-free conditions.
Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE-751 24, Uppsala, Sweden. Johan.Lennartsson@LICR.uu.se
Johan
J
Lennartsson
Fatima
F
Burovic
Barbara
B
Witek
Aleksandra
A
Jurek
Carl-Henrik
CH
Heldin
D000818:Animals; D017209:Apoptosis; D000077214:Becaplermin; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D019061:src-Family Kinases / Q000378:metabolism
D002843:Chromatin; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048054:Mitogen-Activated Protein Kinase 7; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053148:Caspase 3