MAP Kinase activation by receptor tyrosine kinases: in control of cell migration.
A myriad of cellular processes instigated by growth factors are mediated by cell surface-associated receptor tyrosine kinases (RTKs). Subsequent downstream activation of signaling cascades, as well as their crosstalk, endows specificity in terms of the phenotypic outcome, e.g., cellular proliferation, migration, or differentiation. Such signaling diversity is exemplified by the ability of the epidermal growth factor receptor (EGFR) to stimulate different MAPK cascades, especially the ERK1/2 cascade. It has been shown that the ability of the ERK1/2 cascade to specify cell fate, such as cell migration, is dependent on signal duration governed by feedback control. Here we focus on one experimental system, MCF10A human mammary cells, and a phenotypic outcome of cell migration. We present methods to identify key components of underlying cascades and their effects on the migratory phenotype. We focus on profiling activation of signaling modules, as well as transcriptional regulation, emphasizing the high-throughput potential of such approaches.
Tarcic
Gabi
G
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
Yarden
Yosef
Y
D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases