The Pleckstrin Homology Domain Mediates Transformation by Oncogenic Dbl through Specific Intracellular Targeting
The pleckstrin homology (PH) domain is an ~100 amino acid structural motif found in many cellular signaling molecules, including the Dbl oncoprotein and related, putative guanine nucleotide exchange factors (GEFs). Here we have examined the role of the Dbl PH (dPH) domain in the activities of oncoge...
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Published in | The Journal of biological chemistry Vol. 271; no. 32; pp. 19017 - 19020 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
09.08.1996
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Subjects | |
Online Access | Get full text |
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Summary: | The pleckstrin homology (PH) domain is an ~100 amino acid structural motif found in many cellular signaling molecules, including
the Dbl oncoprotein and related, putative guanine nucleotide exchange factors (GEFs). Here we have examined the role of the
Dbl PH (dPH) domain in the activities of oncogenic Dbl. We report that the dPH domain is not involved in the interaction of
Dbl with small GTP-binding proteins and is incapable of transforming NIH 3T3 fibroblasts. On the other hand, co-expression
of the dPH domain with oncogenic Dbl inhibits Dbl-induced transformation. A deletion mutant of Dbl that lacks a significant
portion of the PH domain retains full GEF activity, but is completely inactive in transformation assays. Replacement of the
PH domain by the membrane-targeting sequence of Ras is not sufficient for the recovery of transforming activity. However,
subcellular fractionations of Dbl and Dbl mutants revealed that the PH domain is necessary and sufficient for the association
of Dbl with the Triton X-100-insoluble cytoskeletal components. Thus, our results suggest that the dPH domain mediates cellular
transformation by targeting the Dbl protein to specific cytoskeletal locations to activate Rho-type small GTP-binding proteins. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.271.32.19017 |