Fig. 1.

Signal transduction pathways activated by engagement of the bombesin/GRP receptor, a paradigm of mitogenic GPCR. The binding of the ligand (e.g. bombesin) to the cognate GPCR (e.g. the bombesin/GRP preferring receptor) induces activation of the heterotrimeric G proteins of the Gq and G12 subfamilies. Signaling through Gq/G11 leads to PLC activation, hydrolysis of PIP2, generation of IP3 and DAG, and activation of subsequent phosphorylation cascades leading to the activation of ERKs, p70S6K, and PKD. These pathways are representative of studies in Swiss 3T3 fibroblasts, SCLC cell lines, and pancreatic cancer cells. In other cell types, activation of tyrosine phosphorylation pathways including Src, EGFR, and/or Pyk-2 promote Ras-mediated ERK activation via the SOS–Grb2 complex. Signaling through the G12 subfamily (comprising Gα12 and Gα13) transduces GPCR signals into Rho activation, actin remodeling, assembly of focal adhesions, and tyrosine phosphorylation of the focal adhesion-associated proteins FAK, CAS, and paxillin, and complex formation between FAK and Src. These pathways are implicated in both cell proliferation and cell migration. With permission, from Ref. [12]