THE CELLULAR-RESPONSE TO NEUREGULINS IS GOVERNED BY COMPLEX INTERACTIONS OF THE ERBB RECEPTOR FAMILY

Deregulated signaling by the four members of the epidermal growth fact or receptor tyrosine kinase family (erbB family) is implicated in the genesis or progression of human cancers. However, efforts to analyze s ignaling by these receptors have been hampered by the diversity of lig ands and extensive interreceptor cross talk. We have expressed the fou r human erbB family receptors, Singly and in pairwise combinations, in a pro-B-lymphocyte cell line (Ba/F3) and investigated the range of in teractions activated by the epidermal growth factor homology domain of the agonist neuregulin beta. The results provide the first comprehens ive analysis of the response of this receptor family to a single pepti de agonist. This peptide induced complex patterns of receptor tyrosine phosphorylation and regulation of Ba/F3 cell survival and proliferati on. These data demonstrate the existence of several previously undocum ented receptor interactions driven by neuregulin.