The G-protein-coupled angiotensin II-type 1 (AT1) receptor activates the mitogen-activated protein (MAP) kinase cascade and the Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT) cascade via tyrosine phosphorylation. Recent observations indicated that the G beta -subunit of heterotrimeric G-proteins interacts with tyrosine phosphorylated proteins. We investigated whether angiotensin II (ANG II) activates MAP-kinases and JAK/STAT cascades via the G beta -subunit. In rat aortic smooth muscle (RASM) cells we found phosphorylated proteins associated with the G beta -subunit SHC (Sequence Homology of Collagen) and JAK2. We demonstrate that JAK2 activity increased upon GP-binding. The activity of pp60(c-src) kinase also increased, but upon activation pp60(c-src) dissociates from the G beta -complex. Immunoprecipitations revealed that SHC forms a complex with JAK2. Blockade of JAK2 with AG490 abolished this complex formation; therefore, JAK2 may be the kinase responsible for SHC phosphorylation. Thus, the G beta -subunit may play a pivotal role in AT1-receptor signaling by connecting signaling cascades leading to cell growth and differentiation.