Abstract:
:SH4 domains provide bipartite membrane-targeting signals for oncogenic Src family kinases. Here we report the induction of non-apoptotic plasma membrane (PM) blebbing as a novel and conserved activity of SH4 domains derived from the prototypic Src kinases Src, Fyn, Yes and Lck as well as the HASPB protein of Leishmania parasites. SH4-domain-induced blebbing is highly dynamic, with bleb formation and collapse displaying distinct kinetics. These reorganizations of the PM are controlled by Rho but not Rac or Cdc42 GTPase signalling pathways. SH4-induced membrane blebbing requires the membrane association of the SH4 domain, is regulated by the activities of Rock kinase and myosin II ATPase, and depends on the integrity of F-actin as well as microtubules. Endogenous Src kinase activity is crucial for PM blebbing in SH4-domain-expressing cells, active Src and Rock kinases are enriched in SH4-domain-induced PM blebs, and PM blebbing correlates with enhanced cell invasion in 3D matrices. These results establish a novel link between SH4 domains, Src activity and Rho signalling, and implicate SH4-domain-mediated PM dynamization as a mechanism that influences invasiveness of cells transformed by SH4-domain-containing oncoproteins.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Tournaviti S,Hannemann S,Terjung S,Kitzing TM,Stegmayer C,Ritzerfeld J,Walther P,Grosse R,Nickel W,Fackler OTdoi
10.1242/jcs.011130subject
Has Abstractpub_date
2007-11-01 00:00:00pages
3820-9issue
Pt 21eissn
0021-9533issn
1477-9137pii
120/21/3820journal_volume
120pub_type
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