Adaptor protein Lad relays PDGF signal to Grb2 in lung cells: a tissue-specific PDGF signal transduction

Lad was previously identified as an adaptor protein binding to the SH2 domain of Lck (1). Specific detection of Lad mRNA in lung cells, as well as, in T cells led us to investigate the signaling pathways regulating Lad in lung cells. We found that (i) upon PDGF stimulation, Lad expression is induced in lung cells, especially in the bronchial epithelial cells; (ii) Lad is tyrosine phosphorylated upon PDGF stimulation and is associated with PDGF receptor; (iii) upon PDGF stimulation, Grb2 is recruited to Lad in human embryonic lung cells; (iv) overexpression of Lad elevated AP-1 promoter activity by two- to threefold, whereas dominant negative Lad abrogated PDGF-dependent activation of AP-1 promoter. These results provide a novel mechanism of PDGF-dependent signaling, in which Lad acts as an adaptor in a tissue-specific manner, linking PDGF signal to Grb2 and subsequent activation of AP-1.