The topography and subcellular distribution of mitogen-activated protein kinase kinase 1 (MEK1) in adult rat brain and differentiating PC12 cells

Mitogen-activated protein kinase signal transduction pathway involved in th e regulation of proliferation and differentiation of various mammalian cell s consists of a sequential activation of three protein kinases, Raf, mitoge n-activated protein kinase kinase, and mitogen-activated protein kinase. Th ese kinases are highly expressed in brain and play an important role in neu ronal signalling. In this study, to further characterize mitogen-activated protein kinase signalling pathway in brain, we have elucidated the topograp hy and subcellular distribution of mitogen-activated protein kinase kinase1 in adult rat brain and differentiating PC12 cells. Our immunohistochemical data indicate that mitogen-activated protein kinase kinase1 is widely dist ributed throughout the brain and expressed prominently in cortex, hippocamp us, brainstem, hypothalamus and cerebellum. In these areas of brain mitogen -activated protein kinase kinase1 is exclusively neuronal in origin and is localized within perikarya and dendrites. Confocal microscopy data has dete rmined that a portion of mitogen-activated protein kinase kinase1 in rat br ain is co-localized with microtubules. This co-localization was observed on ly within neuritic shaft and cilia of ventricular ependymal cells. In nerve growth factor-induced differentiating PC12 cells, mitogen-activated protei n kinase kinase1 displays co-localization with microtubules within proximal regions of neuritic shafts and their junctions with the cell somas. From b ovine brain extract, mitogen-activated protein kinase kinase1 co-purifies w ith microtubules. In vitro kinase assay detected mitogen-activated protein kinase kinase1 activity within purified microtubules. These observations indicate that mitogen-activated protein kinase kinase1 i s associated with microtubules within some specialized compartments of the brain and microtubule-associated mitogen-activated protein kinase kinase1 i s catalytically active. (C) 1999 IBRO. Published by Elsevier Science Ltd.