Im. Otto et al., The p150-Spir protein provides a link between c-Jun N-terminal kinase function and actin reorganization, CURR BIOL, 10(6), 2000, pp. 345-348
The Jun N-terminal kinase (INK) Is a downstream effector of pac and Cdc42 G
TPases involved in actin reorganization [1-3]. A role of the Drosophila JNK
homologue, Basket (DJNK/Bsk), in the regulation of cell shape changes and
actin reorganization arises from its function in the process of dorsal clos
ure [4-6]. One potential mechanism for induction of cytoskeletal changes by
JNK is via transcriptional activation of the decapentaplegic gene (dpp, a
member of the TGF beta superfamily) [6]. A direct link between JNK signalli
ng and actin organization has not yet been found, however. We have identifi
ed a novel DJNK-interacting protein, p150-Spir, that belongs to the Wiscott
-Aldrich syndrome protein (WASP) homology domain 2 (WH2) family of proteins
involved in actin reorganization [7,8]. It is a multidomain protein with a
cluster of four WH2 domains, a modified FYVE zinc-finger motif [9], and a
DEJL motif, a docking site for JNK [10], at its carboxy-terminal end, in mo
use fibroblasts, p150-Spir colocalized with F-actin and Its overexpression
induced clustering of filamentous actin around the nucleus. When coexpresse
d with p150-Spir in NIH 3T3 cells, JNK translocated to and colocalizes with
p150-Spir at discrete spots around the nucleus. Carboxy-terminal sequences
of p150-Spir were phosphorylated by JNK both in vitro and in vivo. We conc
lude that p150-spir is a downstream target of JNK function and provides a d
irect link between JNK and actin organization.