Previously, we have demonstrated an ability to stimulate GI UT4medtated glucose transport in an 1RS-1 independent manner in 3 l'3-l.l iidipocytes by o\erexpressing the human epidennal growth factor receptor (LGFR) as a surrogate tyrosine kinase receptor. Using EGFR mutants, we demonstrated a requirement tor autophosphorylation of tyrosine residues on the receptor to stimulate glucose transport. This observation suggests thai signaling molecules that are dependent on EGFR autophosphorylalion. may lie in the signaling pathway to glucose transport. One such molecule, phospholipase C" (PLC) has been implicated by clinical studies of manicdepressive N1DDM patients being treated with lithium, in \\hich there was increased inosttol phosphate levels and increased insulin scnsitiviu. Activation of EGFR expressing adipoeytes with ECil- leads to a 3.Xt 1.4tbld stimulation of phospholipase C activity over basal levels. Forty-five "., inhibition of EG1 -induced PI.C" activity with 50 (iM U73122 resulted in a 44 "i, loss of KGF-induced glucose transport. Furthermore, this inhibition of glucose transport by U73122 was specific as the inactive cogencr. U73343. failed to inhibit 1-GF-induced glucose transport. Insulin stimulated glucose transport activity was similarly inhibited by U7.î \22 |47"ii inhibition). Furthermore, inhibition of PLC activity did not impair KiF-induced activation of glycogen svnthase ( 153.3±I0.5 "n of basal lor control \s. I59.2±20.2 "" ofbasal for 1173122-treated). Preliminary results suggest that inhibition of PLC" activity reduces the amount of GI.UF4 translocated lo the plasma membrane upon hormone stimulation.