The Dbl family of oncogenes

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Abstract

Genetic screening and biochemical studies during the past few years have led to the discovery of a family of cell growth regulatory proteins and oncogene products for which the Dbl oncoprotein is a prototype. These putative guanine nucleotide exchange factors for Rho family small GTP-binding proteins (G proteins) all contain a Dbl homology domain in tandem with a pleckstrin homology domain, and seem to activate specific members of the Rho family of proteins to elicit various biological functions in cells. The Dbl homology domain is directly responsible for binding and activating the small G proteins to mediate downstream signaling events, whereas the pleckstrin homology domain may serve to target these positive regulators of G proteins to specific cellular locations to carry out the signaling task. Despite the increasing interest in the Dbl family of proteins, there is still a good deal to learn regarding the biochemical mechanisms that underlie their diverse biological functions.

Abbreviations

DH Dbl homology
GAP GTPase-activating protien
GEF guanine nucleotide exchange factor
GRF guanine nucleotide release factor
JNK Jun kinase
LPA lysophosphatidic acid
PDGF platelet-derived growth factor
PH pleckstrin homology
PI phosphatidylinositol
PKN protien kinase N
SH Src homology

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Current address: Department of Biochemistry, University of Tennessee, 858 Madison Avenue, Memphis, TN 38163, USA