A tissue restricted role for the Xenopus Jun N-terminal kinase kinase kinase MLK2 in cement gland and pronephric tubule differentiation.
The MLK family of mitogen activated protein kinase kinase kinases (MAPKKK) has been shown to activate Jun N-terminal kinase/stress-activated protein kinase 1 (JNK/SAPK1). However, little is known of the in vivo functions of the MLKs. We have identified a Xenopus laevis MLK that shows highest homology with mammalian MLK2 (62%) and, like MLK2, interacts preferentially with the Rho-family GTPase Rac. xMLK2 was expressed zygotically from late gastrula/early neurula. Surprisingly, this expression was restricted to the cement gland, the brain, and the pronephros. In the differentiating cement gland, xMLK2 expression correlated with cell elongation and the onset of a previously unobserved apoptotic phase, while in the pronephros, expression corresponded with the differentiation and opening of the nephric tubules. Overexpression of xMLK2 in COS7 cells led to a SEK1/MKK4 (MAPKK)-dependent hyperactivation of JNK in response to UV irradiation. xMLK2 was shown to be required for normal cement gland development and pronephric tubule formation using antisense inactivation and a dominant negative xMLK2. The data suggest a novel role for the MLKs as tissue-restricted mediators of signal transduction. They also suggest that tissue-specific responses to common extracellular signals may in part result from the programmed expression of MAPKKKs with differing specificities.
Poitras
Luc
L
Cancer Research Centre and Department of Medical Biology, Laval University, Hôtel-Dieu de Québec, 11 côte du Palais, G1R 2J6 Québec, Canada.
Bisson
Nicolas
N
Islam
Nazrul
N
Moss
Tom
T
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D019556:COS Cells; D002454:Cell Differentiation; D019204:GTP-Binding Proteins / Q000378:metabolism; D007668:Kidney / Q000196:embryology*; D016350:Leucine Zippers; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology*
D029867:Xenopus Proteins; D020930:MAP Kinase Kinase Kinases; C490540:map3k10 protein, Xenopus; D019204:GTP-Binding Proteins