PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2

J de Rooij, N M Boenink, M van Triest, R H Cool, A Wittinghofer, J L Bos

OnderzoeksoutputAcademicpeer review

105 Citaten (Scopus)
14 Downloads (Pure)


The small GTPase Rap1 has been implicated in a variety of cellular processes including the control of cell morphology, proliferation, and differentiation. Stimulation of a large variety of cell surface receptors results in the rapid activation of Rap1, i.e. an increase in the GTP-bound form. This activation is mediated by second messengers like calcium, cAMP, and diacylglycerol, but additional pathways may exist as well. Here we describe a ubiquitously expressed guanine nucleotide exchange factor of 200 kDa that activates Rap1 both in vivo and in vitro. This exchange factor has two putative regulatory domains: a domain with an amino acid sequence related to cAMP-binding domains and a PDZ domain. Therefore, we named it PDZ-GEF1. PDZ-GEFs are closely related to Epacs, Rap-specific exchange factors with a genuine cAMP binding site, that are directly regulated by cAMP. The domain related to cAMP-binding domains, like the cAMP binding site in Epac, serves as a negative regulatory domain. However, PDZ-GEF1 does not interact with cAMP or cGMP. Interestingly, PDZ-GEF1 also activates Rap2, a close relative of Rap1. This is the first example of an exchange factor acting on Rap2. We conclude that PDZ-GEF1 is a guanine nucleotide exchange factor, specific for Rap1 and Rap2, that is controlled by a negative regulatory domain.

Originele taal-2English
Pagina's (van-tot)38125-38130
Aantal pagina's6
TijdschriftThe Journal of Biological Chemistry
Nummer van het tijdschrift53
StatusPublished - 31-dec-1999
Extern gepubliceerdJa

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