STIMULATION OF TYROSINE PHOSPHORYLATION OF A BRAIN PROTEIN BY HIBERNATION

Mammalian hibernation is a state of natural tolerance to severely decr eased brain blood flow. As protein tyrosine phosphorylation is believe d to be involved in the development of resistance to potentially cell- damaging insults, we used immunoblotting for the phosphotyrosine moiet y to analyze extracts from various tissues of hibernating and nonhiber nating ground squirrels. A single, hibernation-specific phosphoprotein was detected in the brain, but not in any other tissue tested. This p rotein: designated pp98 to reflect its apparent molecular weight, is d istributed throughout the brain, and is associated with the cellular m embrane fraction. The presence of the protein is tightly linked to the hibernation state; it is not present in contemporaneously assayed ani mals that are exposed to the same cold temperature as the hibernators, is present for the duration of a hibernation bout (tested from 1 to 1 4 days), and disappears within 1 hour of arousal from hibernation. The close association of pp98 with the hibernation state, its presence in cellular membranes, and the known properties of membrane phosphotyros ine proteins suggest that it may transduce a signal for adaptation to the limited availability of oxygen and glucose and low cellular temper ature that characterizes hibernation in the ground squirrel.