DOI: 10.1016/s0014-5793(97)00309-8. Activation of the exchange factor Ras‐GRF by calcium requires an intact Dbl homology domain

Activation of the exchange factor Ras‐GRF by calcium requires an intact Dbl homology domain

10.1016/s0014-5793(97)00309-8

Crossref journal-article

Wiley

FEBS Letters (311)

Abstract

Ras‐GRF is a guanine nucleotide exchange factor that activates Ras proteins. Its activity on Ras in cells is enhanced upon calcium influx. Activation follows calcium‐induced binding of calmodulin to an IQ motif near the N‐terminus of Ras‐GRF. Ras‐GRF also contains a Dbl homology (DH) domain C‐terminal to the IQ motif. In many proteins, DH domains act as exchange factors for Rho‐GTPase family members. However, we failed to detect exchange activity of this domain on well characterized Rho family members. Instead, we found that mutations analogous to those that block exchange activity of Dbl prevented Ras‐GRF activation by calcium/calmodulin in vivo. All DH domains are followed immediately by a pleckstrin homology (PH) domain. We found that a mutation at a conserved site within the PH domain following the DH domain also prevented Ras‐GRF activation by calcium in vivo. These results suggest that in addition to playing a role as activators of Rho proteins, DH domains can also contribute to the coupling of cellular signals to Ras activation.

Bibliography

Freshney, N. W., Goonesekera, S. D., & Feig, L. A. (1997). Activation of the exchange factor RasâGRF by calcium requires an intact Dbl homology domain. FEBS Letters, 407(1), 111â115. Portico.

Authors 3

Norman W. Freshney (first)
Sunali D. Goonesekera (additional)
Larry A. Feig (additional)

References 40 Referenced 46

Dates

Type	When
Created	23 years ago (July 25, 2002, 8:19 a.m.)
Deposited	1 year, 11 months ago (Sept. 15, 2023, 9:29 p.m.)
Indexed	1 month, 2 weeks ago (July 5, 2025, 12:06 a.m.)
Issued	28 years, 4 months ago (April 21, 1997)
Published	28 years, 4 months ago (April 21, 1997)
Published Online	27 years, 9 months ago (Nov. 7, 1997)
Published Print	28 years, 4 months ago (April 21, 1997)

Funders 0

None

BibTeX

@article{Freshney_1997, title={Activation of the exchange factor Ras‐GRF by calcium requires an intact Dbl homology domain}, volume={407}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/s0014-5793(97)00309-8}, DOI={10.1016/s0014-5793(97)00309-8}, number={1}, journal={FEBS Letters}, publisher={Wiley}, author={Freshney, Norman W. and Goonesekera, Sunali D. and Feig, Larry A.}, year={1997}, month=apr, pages={111–115} }

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