Journal of Cell Science 116, e305-e305 (2003)
Copyright © 2003 The Company of Biologists Limited
...and separating signalling and ruffling
The protooncogene product Cb1 combines an E3 ubiquitin ligase with an
adaptor protein. It is critical for ubiquitylation-dependent endocytosis of
several receptors and also binds to a variety of downstream signalling
molecules, negatively regulating signalling. Robin Scaife and co-workers now
add growth-factor-induced actin ruffling to the list of processes that this
`multi-adaptor' protein controls (see p.
463). They demonstrate that expression of a dominant negative Cb1
mutant (480-Cb1) that lacks the C-terminal sequences that bind to signalling
molecules strongly enhances actin ruffling induced by platelet-derived growth
factor (PDGF). They also show that 480-Cb1 increases activation of the small
GTPase Rac, which is known to regulate actin ruffling. Significantly, 480-Cb1
does not affect activation of signalling molecules participating in
PDGF-dependent mitogenic signalling (e.g. MAP kinase and PI 3-kinase) despite
requiring Rac, Src and PI 3-kinase for its effect on ruffling. Since Scaife
and co-workers observe translocation of wild-type Cb1 to sites of actin
nucleation where actin ruffles form, they conclude that it is this subcellular
targeting that allows Cb1 to regulate cytoskeletal rearrangements without
affecting mitogenic signalling.
Related articles in JCS:
- The multi-adaptor proto-oncoprotein Cbl is a key regulator of Rac and actin assembly
- Robin M. Scaife, Sara A. Courtneidge, and Wallace Y. Langdon
JCS 2003 116: 463-473.
[Abstract]
[Full Text]
