Previous Article | Next Article 
Molecular and Cellular Biology, July 2000, p. 4736-4744, Vol. 20, No. 13
Department of
Pharmacology1 and Department of Cell
Biology,2 Skirball Institute of Biomolecular
Medicine, New York University Medical Center, New York, New York
Received 29 November 1999/Returned for modification 20 February
2000/Accepted 27 March 2000
We have previously shown that the Ste20 kinase encoded by
misshapen (msn) functions upstream of the c-Jun
N-terminal kinase (JNK) mitogen-activated protein kinase module in
Drosophila. msn is required to activate the
Drosophila JNK, Basket (Bsk), to promote dorsal closure of
the embryo. A mammalian homolog of Msn, Nck interacting kinase,
interacts with the SH3 domains of the SH2-SH3 adapter protein Nck. We
now show that Msn likewise interacts with Dreadlocks (Dock), the
Drosophila homolog of Nck. dock is required for
the correct targeting of photoreceptor axons. We have performed a
structure-function analysis of Msn in vivo in Drosophila in order to elucidate the mechanism whereby Msn regulates JNK and to
determine whether msn, like dock, is required
for the correct targeting of photoreceptor axons. We show that Msn
requires both a functional kinase and a C-terminal regulatory domain to
activate JNK in vivo in Drosophila. A mutation in a PXXP
motif on Msn that prevents it from binding to the SH3 domains of Dock
does not affect its ability to rescue the dorsal closure defect in
msn embryos, suggesting that Dock is not an upstream
regulator of msn in dorsal closure. Larvae with only this
mutated form of Msn show a marked disruption in photoreceptor axon
targeting, implicating an SH3 domain protein in this process; however,
an activated form of Msn is not sufficient to rescue the
dock mutant phenotype. Mosaic analysis reveals that
msn expression is required in photoreceptors in order for
their axons to project correctly. The data presented here genetically
link msn to two distinct biological events, dorsal closure
and photoreceptor axon pathfinding, and thus provide the first evidence
that Ste20 kinases of the germinal center kinase family play a role in
axonal pathfinding. The ability of Msn to interact with distinct
classes of adapter molecules in dorsal closure and photoreceptor axon
pathfinding may provide the flexibility that allows it to link to
distinct upstream signaling systems.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
The Ste20 Kinase Misshapen Regulates Both
Photoreceptor Axon Targeting and Dorsal Closure, Acting Downstream
of Distinct Signals
*
Corresponding author. Mailing address for Edward
Skolnik: New York University Medical Center, Department of
Pharmacology, Skirball Institute of Biomolecular Medicine, 540 First
Ave., New York, NY 10016. Phone: (212) 263-7458. Fax: (212) 263-5711. E-mail: Skolnik{at}saturn.med.nyu.edu. Mailing address
for Jessica Treisman: New York University Medical Center, Department of
Cell Biology, Skirball Institute of Biomolecular Medicine, 540 First
Ave., New York, NY 10016. Phone: (212) 263-1031. Fax: (212)
263-7760. E-mail: Treisman{at}saturn.med.nyu.edu.
Molecular and Cellular Biology, July 2000, p. 4736-4744, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Balakireva, M., Rosse, C., Langevin, J., Chien, Y.-c., Gho, M., Gonzy-Treboul, G., Voegeling-Lemaire, S., Aresta, S., Lepesant, J.-A., Bellaiche, Y., White, M., Camonis, J.
(2006). The Ral/Exocyst Effector Complex Counters c-Jun N-Terminal Kinase-Dependent Apoptosis in Drosophila melanogaster. Mol. Cell. Biol.
26: 8953-8963
[Abstract] [Full Text] -
Baumgartner, M., Sillman, A. L., Blackwood, E. M., Srivastava, J., Madson, N., Schilling, J. W., Wright, J. H., Barber, D. L.
(2006). The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors. Proc. Natl. Acad. Sci. USA
103: 13391-13396
[Abstract] [Full Text] -
Koppen, M., Fernandez, B. G., Carvalho, L., Jacinto, A., Heisenberg, C.-P.
(2006). Coordinated cell-shape changes control epithelial movement in zebrafish and Drosophila.. Development
133: 2671-2681
[Abstract] [Full Text] -
Shakir, M. A., Gill, J. S., Lundquist, E. A.
(2006). Interactions of UNC-34 Enabled With Rac GTPases and the NIK Kinase MIG-15 in Caenorhabditis elegans Axon Pathfinding and Neuronal Migration. Genetics
172: 893-913
[Abstract] [Full Text] -
Hu, Y., Leo, C., Yu, S., Huang, B. C. B., Wang, H., Shen, M., Luo, Y., Daniel-Issakani, S., Payan, D. G., Xu, X.
(2004). Identification and Functional Characterization of a Novel Human Misshapen/Nck Interacting Kinase-related Kinase, hMINK{beta}. J. Biol. Chem.
279: 54387-54397
[Abstract] [Full Text] -
Bladt, F., Aippersbach, E., Gelkop, S., Strasser, G. A., Nash, P., Tafuri, A., Gertler, F. B., Pawson, T.
(2003). The Murine Nck SH2/SH3 Adaptors Are Important for the Development of Mesoderm-Derived Embryonic Structures and for Regulating the Cellular Actin Network. Mol. Cell. Biol.
23: 4586-4597
[Abstract] [Full Text] -
Wright, J. H., Wang, X., Manning, G., LaMere, B. J., Le, P., Zhu, S., Khatry, D., Flanagan, P. M., Buckley, S. D., Whyte, D. B., Howlett, A. R., Bischoff, J. R., Lipson, K. E., Jallal, B.
(2003). The STE20 Kinase HGK Is Broadly Expressed in Human Tumor Cells and Can Modulate Cellular Transformation, Invasion, and Adhesion. Mol. Cell. Biol.
23: 2068-2082
[Abstract] [Full Text] -
Xue, Y, Wang, X, Li, Z, Gotoh, N, Chapman, D, Skolnik, E.
(2001). Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase (NIK). Development
128: 1559-1572
[Abstract]
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»