Novel human Ste20-related kinase Mst4 is biologically active in the activation of MEK/ERK pathway and in mediating cell growth and transformation. It is pro apoptotic and is highly expressed in placenta, thymus, and peripheral blood leukocytes. Interaction with Golgi matrix protein GOLGA2 results in autophosphorylation on Thr-178, possibly as a consequence of stabilization of dimer formation. This may also be activated by C terminal cleavage. MST3 or Mammalian Sterile 20-like kinase 3 is a member of the germinal center kinase-III family. MST3 contains a conserved kinase domain at its NH(2)-terminus and a regulatory domain at its COOH-terminus. Caspase-mediated cleavage of the regulatory domain of MST3 activates its intrinsic kinase activity and leads to nuclear translocation. Expression of COOH-terminal truncated MST3 in cells results in DNA fragmentation and induction of apoptosis. It can inhibit cell migration in a fashion dependent on autophosphorylation and can regulate paxillin phosphorylation through tyrosine phosphatase PTP-PEST. Mitogen activated protein kinase cascades have been conserved throughout evolution. In mammals, these cascades allow responses to complex stimuli such as growth factors and inflammatory cytokines. In yeast, STK25 functions upstream of the MAPK cascade.