abl kinase inhibits the engulfment of apopotic cells in caenorhabditis elegansabl激酶抑制apopotic细胞线虫的吞没.pdfVIP

PLoS BIOLOGY Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans 1,2 3¤a 1¤b 1 3,4 1* Michael E. Hurwitz , Pamela J. Vanderzalm , Laird Bloom , Julia Goldman , Gian Garriga , H. Robert Horvitz 1 Howard Hughes Medical Institute (HHMI), Department of Biology, MIT, Cambridge, Massachusetts, United States of America, 2 Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States of America, 3 Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America, 4 Helen Wills Neuroscience Institute, University of California, Berkeley, California, United States of America The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway includes the adaptor protein CED-2 CrkII and the small GTPase CED-10 Rac, and acts to rearrange the cytoskeleton of the engulfing cell. The other pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Although many components required for engulfment have been identified, little is known about inhibition of engulfment. The tyrosine kinase Abl regulates the actin cytoskeleton in mammals and Drosophila in multiple ways. For example, Abl inhibits cell migration via phosphorylation of CrkII. We tested whether ABL-1, the C. elegans ortholog of Abl, inhibits the CED-2 CrkII-dependent engulfment of apoptotic cells. Our genetic