Cyclin dependent kinase 5 (Cdk5) mediated inhibition of the MAP kinase pathway results in CREB down regulation and apoptosis in PC12 cells.
Cyclin dependent kinase 5 (cdk5) is active mainly in postmitotic cells like neurons and regulates important cellular functions by phosphorylating a wide variety of targets. Nerve growth factor stimulates the MEK-ERK MAP kinase pathway and causes neuronal differentiation and survival. It was reported previously that Cdk5 inhibits the MAP kinase pathway by phosphorylating Map kinase kinase-1 (MEK1) [1]. We have delineated the functional consequence of this cross talk and found that the cdk5 mediated inhibition of MEK1 results in apoptosis. We also demonstrate that the activity of transcription factor CREB, which is known to play pro-survival roles in neuronal cells, is attenuated as a result of this cross-talk.
Sharma
Monica
M
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India. monicavrinda@gmail.com
Hanchate
Naresh Kumar
NK
Tyagi
Rakesh K
RK
Sharma
Pushkar
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D015536:Down-Regulation; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016716:PC12 Cells; D010770:Phosphotransferases / Q000378:metabolism*; D051381:Rats
C492235:Cdk5r1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat