SERUM-INDUCED TRANSLOCATION OF MITOGEN-ACTIVATED PROTEIN-KINASE TO THE CELL-SURFACE RUFFLING MEMBRANE AND THE NUCLEUS

The mitogen-activated protein (MAP) kinase signal transduction pathway represents an important mechanism by which growth factors regulate ce ll function. Targets of the MAP kinase pathway are located within seve ral cellular compartments. Signal transduction therefore requires the localization of MAP kinase in each sub-cellular compartment that conta ins physiologically relevant substrates. Here, we show that serum trea tment causes the translocation of two human MAP kinase isoforms, p40ma pk and p41mapk, from the cytosol into the nucleus. In addition, we rep ort that p41mapk (but not p40mapk) is localized at the cell surface ru ffling membrane in serum-treated cells. To investigate whether the pro tein kinase activity of MAP kinase is required for serum-induced redis tribution within the cell, we constructed mutated kinase-negative form s of p40mapk and p41mapk. The kinase-negative MAP kinases were not obs erved to localize to the cell surface ruffling membrane. In contrast, the kinase-negative MAP kinases were observed to be translocated to th e nucleus. Intrinsic MAP kinase activity is therefore required only fo r localization at the cell surface and is not required for transport i nto the nucleus. Together, these data demonstrate that the pattern of serum-induced redistribution of p40mapk is different from p41mapk. Thu s, in addition to common targets of signal transduction, it is possibl e that these MAP kinase isoforms may differentially regulate targets l ocated in distinct sub-cellular compartments.