Mitogen-activated protein kinases and signal transduction in myeloid cells

Most cells are organized into cooperative assemblies called ''tissues'' and are in contact with the extracellular matrix, a complex network of extracellular macromolecules. Typically, cells are maintained in place by direct cell-cell adhesions or form mechanical attachment forces to generate movement. Cell migration is crucial in many situations: during development for cells to settle in precisely defined locations, in cancer metastasis when tumor cells enter the blood flow and migrate to another site to establish a secondary tumor; in immunity where trafficking of lymphocytes educate memory cells and patrol the body; and in inflammation where mature myeloid cells interact with the endothelium to leave the capillaries and migrate into the tissues toward the site of infection. Cells renew themselves (i.e., proliferate) and change their characteristics (i.e., differentiate), resulting in the production of specific sets of new proteins. These processes occur in response to the cell environment and are influenced by signals to the cell generated through contact with the extracellular matrix. Under similar influence by extracellular signals, differentiated cells can carry out their own death through activation of an internally encoded suicide program that initiates a characteristic form of cell death called ''apoptosis.'' Apoptosis is identified Is by morphologic characteristics (i.e., cellular shrinkage, chromosome condensation and chromatin fragmentation) that are distinguishable from those seen during necrosis, brought about by injury. Therefore, apoptosis contributes to many cellular processes and could be considered as a normal physiologic process controlling homeostasis. in addition, changes in the balance between cell survival and cell death might participate in the pathogenesis of various diseases. Thus, cells grow, divide, differentiate and die and during their life time, they receive signals from many molecules that are either secreted by neighboring cells, released by diffusion or bound to the extracellular matrix or the surface of another cell. These multiple signals must be integrated by the cells, programmed to respond selectively by either proliferating, differentiating or carrying on some specialized function. The mechanisms by which cell-cell contact or interaction with signaling molecules induce specific changes in cellular processes and gene expression are referred to as ''signal transduction pathways.'' This review will focus on one such pathway, the mitogen-activated protein kinase cascade that was recently unraveled in many cell types, including myeloid cells.