The topography and subcellular distribution of mitogen-activated protein kinase kinase1 (MEK1) in adult rat brain and differentiating PC12 cells.
Mitogen-activated protein kinase signal transduction pathway involved in the regulation of proliferation and differentiation of various mammalian cells consists of a sequential activation of three protein kinases, Raf, mitogen-activated protein kinase kinase, and mitogen-activated protein kinase. These kinases are highly expressed in brain and play an important role in neuronal signalling. In this study, to further characterize mitogen-activated protein kinase signalling pathway in brain, we have elucidated the topography and subcellular distribution of mitogen-activated protein kinase kinasel in adult rat brain and differentiating PC12 cells. Our immunohistochemical data indicate that mitogen-activated protein kinase kinase1 is widely distributed throughout the brain and expressed prominently in cortex, hippocampus, brainstem, hypothalamus and cerebellum. In these areas of brain mitogen-activated protein kinase kinasel is exclusively neuronal in origin and is localized within perikarya and dendrites. Confocal microscopy data has determined that a portion of mitogen-activated protein kinase kinase1 in rat brain is co-localized with microtubules. This co-localization was observed only within neuritic shaft and cilia of ventricular ependymal cells. In nerve growth factor-induced differentiating PC12 cells, mitogen-activated protein kinase kinase1 displays co-localization with microtubules within proximal regions of neuritic shafts and their junctions with the cell somas. From bovine brain extract, mitogen-activated protein kinase kinasel co-purifies with microtubules. In vitro kinase assay detected mitogen-activated protein kinase kinase1 activity within purified microtubules. These observations indicate that mitogen-activated protein kinase kinase1 is associated with microtubules within some specialized compartments of the brain and microtubule-associated mitogen-activated protein kinase kinase1 is catalytically active.
Schipper
H M
HM
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, and Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Agarwal-Mawal
A
A
Paudel
H K
HK
D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000033:anatomy & histology* / Q000201:enzymology*; D019085:Fluorescent Antibody Technique, Direct; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D048369:MAP Kinase Kinase 1; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects / Q000201:enzymology; D020929:Mitogen-Activated Protein Kinase Kinases; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure*; D016716:PC12 Cells; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology / Q000648:ultrastructure
D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases