The germinal center kinase GCK-1 is a negative regulator of MAP kinase activation and apoptosis in the C. elegans germline.
The germinal center kinases (GCK) constitute a large, highly conserved family of proteins that has been implicated in a wide variety of cellular processes including cell growth and proliferation, polarity, migration, and stress responses. Although diverse, these functions have been attributed to an evolutionarily conserved role for GCKs in the activation of ERK, JNK, and p38 MAP kinase pathways. In addition, multiple GCKs from different species promote apoptotic cell death. In contrast to these paradigms, we found that a C. elegans GCK, GCK-1, functions to inhibit MAP kinase activation and apoptosis in the C. elegans germline. In the absence of GCK-1, a specific MAP kinase isoform is ectopically activated and oocytes undergo abnormal development. Moreover, GCK-1- deficient animals display a significant increase in germ cell death. Our results suggest that individual germinal center kinases act in mechanistically distinct ways and that these functions are likely to depend on organ- and developmental-specific contexts.
Schouest
Katherine R
KR
Department of Genetics, The University of MD Anderson Cancer Center, Houston, Texas, United States of America.
Kurasawa
Yasuhiro
Y
Furuta
Tokiko
T
Hisamoto
Naoki
N
Matsumoto
Kunihiro
K
Schumacher
Jill M
JM
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D000081410:Germinal Center Kinases; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference
D029742:Caenorhabditis elegans Proteins; C546116:GCK-1 protein, C elegans; D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; C085697:mpk-1 protein, C elegans