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Molecular and Cellular Biology, November 2002, p. 7658-7666, Vol. 22, No. 21
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.21.7658-7666.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Drosophila PDZ-GEF, a Guanine Nucleotide Exchange Factor for Rap1 GTPase, Reveals a Novel Upstream Regulatory Mechanism in the Mitogen-Activated Protein Kinase Signaling Pathway

Jun Hee Lee, Kyoung Sang Cho, Jihyun Lee, Dohoon Kim, Sung-Bae Lee, Jungsik Yoo, Guang-Ho Cha, and Jongkyeong Chung*

National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, Korea

Received 23 January 2002/ Returned for modification 29 March 2002/ Accepted 23 July 2002

PDZ-GEF is a novel guanine nucleotide exchange factor for Rap1 GTPase. Here we isolated Drosophila melanogaster PDZ-GEF (dPDZ-GEF), which contains the all-conserved domains of mammalian and nematode PDZ-GEF including cyclic nucleotide monophosphate-binding, Ras exchange motif, PDZ, RA, and GEF domains. dPDZ-GEF loss-of-function mutants were defective in the development of various organs including eye, wing, and ovary. Many of these phenotypes are strikingly similar to the phenotype of the rolled mutant, implying that dPDZ-GEF functions upstream of the mitogen-activated protein (MAP) kinase pathway. Indeed, we found that dPDZ-GEF is specifically involved in photoreceptor cell differentiation, facilitating its neuronal fate via activation of the MAP kinase pathway. Rap1 was found to link dPDZ-GEF to the MAP kinase pathway; however, Ras was not involved in the regulation of the MAP kinase pathway by dPDZ-GEF and actually had an inhibitory function. The analyses of ovary development in dPDZ-GEF-deficient mutants also demonstrated another role of dPDZ-GEF independent of the MAP kinase signaling pathway. Collectively, our findings identify dPDZ-GEF as a novel upstream regulator of various morphogenetic pathways and demonstrate the presence of a novel, Ras-independent mechanism for activating the MAP kinase signaling pathway.

* Corresponding author. Mailing address: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-Dong, Yusong, Taejon 305-701, Republic of Korea. Phone: 82-42-869-2620. Fax: 82-42-869-2610. E-mail: jchung{at}mail.kaist.ac.kr.

Molecular and Cellular Biology, November 2002, p. 7658-7666, Vol. 22, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.21.7658-7666.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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