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. (C) 2007 Elsevier Inc. All rights reserved.