THE TRANSCRIPTION FACTOR CREB IS NOT PHOSPHORYLATED AT SERINE-133 IN AXOTOMIZED NEURONS - IMPLICATIONS FOR THE EXPRESSION OF AP-1 PROTEINS

The present study has investigated whether nerve fiber transection alt ers the phosphorylation of serine at position 133 (Ser(133)) of the tr anscription factor CREB (phosphoCREB). Activation of CREB by phosphory lation has a major function in the control of gene transcription. Phos phoCREB was visualized by antisera that specificly react with an epito pe comprising the phosphorylated Ser(133) of CREB as well as of CREM a nd ATF1 proteins. In untreated rats, nuclear immunoreactivity (IR) of phosphoCREB was consistently visible, e.g. in the cortex, thalamic and hypothalamic compartments and central termination areas of primary so matosensory afferents. Transection of peripheral (sciatic nerve), cran ial (hypogrossal and facial nerve) and central (medial forebrain bundl e and mammillo-thalamic tract) nerve fibers did not increase phosphoCR EB-IR in the axotomized neurons between 5 min and 30 days post-axotomy . In contrast, phosphoCREB-IR appeared after 24 h in glial cells adjac ent to the axotomized motoneurons and persisted up to 4 weeks. This in crease in glial phosphoCREB-IR was paralleled by enhanced expression o f the CREB protein itself. Between 20 min and 24 h following sciatic n erve transection, the number of phosphoCREB labeled nuclei also increa sed in neurons of the ipsilateral superficial dorsal horn of lumbar L3 -L5 spinal cord segments. These data suggest that phosphorylation of S er(133) in CREB/CREM/ATF1 proteins is not involved in the transcriptio nal control of early-response genes such as c-jun in axotomized neuron s following nerve transection. This is in contrast to the reported pho sphorylation of CREB and its Irans-acting effects on immediate-early g enes such as c-fos after transynaptic neuronal excitation.