Differential regulation of the regulatory subunits for phosphatidylinositol 3-kinase in response to motor nerve injury.

Type Ia phosphatidylinositol 3-kinase (PI3K) generates lipid products that operate as one of major second messengers following activation of tyrosine kinase receptors. PI3K is a heterodimer composed of a 110-kDa catalytic subunit and a regulatory subunit. In this study, we determined the expression of mRNA for the regulatory subunits after injury of rat hypoglossal nerves. In situ hybridization histochemistry revealed that the expression of PI3K regulatory subunit alpha isoforms (p85alpha, p55alpha, and p50alpha) was significantly enhanced in injured motor neurons, whereas other regulatory subunits such as p85beta or p55gamma were not detected. Of the alpha isoforms, the greatest increase was observed in p55alpha mRNA levels, while there were smaller increases in p85alpha and p50alpha mRNA expression. These results were confirmed by RT-PCR analysis. Further immunohistochemical analysis also confirmed the increased level of p55alpha protein in injured motor neurons. Taken together with the previously reported induction of the p110alpha catalytic subunit in injured neurons, these results suggest that PI3K, consisting of p55alpha and p110alpha, plays a crucial role in the process of nerve regeneration.