Figure 3

Pathways involved in mesenchymal cell proliferation and differentiation induced by G protein coupled receptors (GPCRs). G protein coupled muscarinic receptors activate signaling cascades resulting in p42/p44 MAP kinase (MAPK), Rho-kinase and phosphatidyl-inositol-3-kinase (PI3K) activity. In addition, the signaling output of receptor tyrosine kinases (RTKs) is enhanced. Activation of the PI3K pathway appears to be particularly important in mesenchymal cell proliferation and differentiation. With Akt and mammalian target of rapamycin (mTOR) as signaling intermediates, PI3K activates p70S6K, which is involved in ribosome mediated protein translation. p42/p44 MAPK, activated by the sequential activation of Ras, Raf and MEK, also activates p70S6K and plays an important role in the induction of transcription factors involved in cell cycle progression. Rho-kinase activated transcription factors also play a central role in smooth muscle specific gene transcription, ultimately mediating the accumulation of contractile and contraction regulatory proteins. See the text for further detail.