RT Journal Article
ID 7357906141591275
A1 Miyake, Sachiko
A1 Lupher, Jr., Mark L.
A1 Andoniou, Christopher E.
A1 Lill, Nancy L.
A1 Ota, Satoshi
A1 Douillard, Patrice
A1 Rao, Navin
A1 Band, Hamid
T1 The Cbl Protooncogene Product: From an Enigmatic Oncogene to Center Stage of Signal Transduction
JF Critical Reviews™ in Oncogenesis
JO CRO
YR 1997
FD 1997-09-01
VO 8
IS 2-3
SP 189
OP 218
K1 protooncogenes
K1 protein-tyrosine kinase
K1 receptors
K1 oncogenesis
K1 Src-homology domains
K1 phosphotyrosine-binding domains
K1 Ras.
AB The c-cbl protooncogene was first identified as the cellular homologue of a viral oncogene ν-cbl that induces pre-B lymphomas and myeloid leukemias in mice. Until recently, the biochemical basis for Cbl's transforming potential and its physiological role remained unclear. However, a convergence of biochemical studies in mammalian cells and genetic studies in C. elegans and Drosophila has now identified Cbl as a negative regulator of tyrosine kinase signaling. The N-terminal transforming region of Cbl (Cbl-N) and an adjacent RING finger domain are the elements most conserved during evolution. The Cbl-N region has now been shown to contain a novel phosphotyrosine-binding (PTB) domain that directly interacts with autophosphorylated tyrosine kinases via a D(N/D)XpY motif. A critical role of the PTB domain in Cbl function is demonstrated by the localization of a loss-of-function mutation in C. elegans Cbl homologue SLI-1 within this region. The corresponding mutation in human Cbl inactivates the PTB domain function and abrogates Cbl-mediated regulation of tyrosine kinase function. Recent studies have also identified a novel signaling pathway initiated by the interaction of mammalian Cbl proteins with the SH2 domains of Crk adaptor molecules, which results in Cbl's linkage with C3G, a guanine nucleotide exchange protein for Rap l family of small G-proteins. Presently, Rap l is thought to antagonize Ras function, although Rap l-specific targets have emerged recently. Thus, recent advances have firmly placed the little known protooncoprotein Cbl on the center stage of tyrosine kinase-mediated signal transduction.
PB Begell House
LK https://www.dl.begellhouse.com/journals/439f422d0783386a,703283381dd19c5b,7357906141591275.html