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 cell function. Targets of the MAP kinase pathway are located within several cellular compartments. Signal transduction therefore requires the localization of MAP kinase in each sub-cellular compartment that contains physiologically relevant substrates. Here, we show that serum treatment causes the translocation of two human MAP kinase isoforms, p40mapk and p41mapk, from the cytosol into the nucleus. In addition, we report that p41mapk (but not p40mapk) is localized at the cell surface ruffling membrane in serum-treated cells. To investigate whether the protein kinase activity of MAP kinase is required for serum-induced redistribution within the cell, we constructed mutated kinase-negative forms of p40mapk and p41mapk. The kinase-negative MAP kinases were not observed to localize to the cell surface ruffling membrane. In contrast, the kinase-negative MAP kinases were observed to be translocated to the nucleus. Intrinsic MAP kinase activity is therefore required only for localization at the cell surface and is not required for transport into the nucleus. Together, these data demonstrate that the pattern of serum-induced redistribution of p40mapk is different from p41mapk. Thus, in addition to common targets of signal transduction, it is possible that these MAP kinase isoforms may differentially regulate targets located in distinct sub-cellular compartments.
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605.
F A
FA
Gonzalez
A
A
Seth
D L
DL
Raden
D S
DS
Bowman
F S
FS
Fay
R J
RJ
Davis
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001798:Blood Proteins / Q000494:pharmacology*; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D002467:Cell Nucleus / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D003600:Cytosol / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D007091:Image Processing, Computer-Assisted; D007536:Isomerism; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000032:analysis / Q000235:genetics / Q000493:pharmacokinetics*; D015398:Signal Transduction / Q000502:physiology; D014178:Translocation, Genetic
D001798:Blood Proteins; D004247:DNA; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases