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Germinal centre kinase is a 97 kDa mammalian Ste20 homologue that specifically activates the SAPK/JNK pathway. Activation is blocked by dominant-negative mutants of SEK (SEK-AL) but GCK does not directly phosphorylate SEK nor MEKK. Instead, GCK requires the action of MLK-3 (or a related MLK) to induce this pathway.
Regulation of GCK (or the related enzymes HPK and GLK) is unclear but there is recent evidence that GCK can couple TRAF2 (a TNF receptor interacting protein) to SAPK activation.
References
- Katz, P., Whalen, G. and Kehrl, J.H. (1994) Differential expression of a novel protein kinase in human B lymphocytes. Preferential localization in the germinal center. J.Biol. Chem. 269 16802-16809
- Pombo, C., Kehrl, J.H., Sanchez, I., Katz, P., Avruch, J., Zon, L.I., Woodgett, J.R., Force, T. and Kyriakis, J.M. (1995) Activation of the SAP kinase pathway by germinal centre kinase, a human STE20 homolog. Nature 377,750-754.
- Yuasa, T., Ohno, S., Kehrl, J.H. and Kyriakis, J.M. (1998) Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. J. Biol. Chem. 273, 22681
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