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- Title
Reversible phosphorylation as a molecular switch to regulate plasma membrane targeting of acylated SH4 domain proteins.
- Authors
Tournaviti, Stella; Pietro, Enrica San; Terjung, Stefan; Schafmeier, Tobias; Wegehingel, Sabine; Ritzerfeld, Julia; Schulz, Juliane; Smith, Deborah F; Pepperkok, Rainer; Nickel, Walter
- Abstract
Acylated SH4 domains represent N-terminal targeting signals that anchor peripheral membrane proteins such as Src kinases in the inner leaflet of plasma membranes. Here we provide evidence for a novel regulatory mechanism that may control the levels of SH4 proteins being associated with plasma membranes. Using a fusion protein of the SH4 domain of Leishmania HASPB and GFP as a model system, we demonstrate that threonine 6 is a substrate for phosphorylation. Substitution of threonine 6 by glutamate (to mimic a phosphothreonine residue) resulted in a dramatic redistribution from plasma membranes to intracellular sites with a particular accumulation in a perinuclear region. As shown by both pharmacological inhibition and RNAi-mediated down-regulation of the threonine/ serine-specific phosphatases PP1 and PP2A, recycling back to the plasma membrane required dephosphorylation of threonine 6. We provide evidence that a cycle of phosphorylation and dephosphorylation may also be involved in intracellular targeting of other SH4 proteins such as the Src kinase Yes.
- Publication
Traffic (Copenhagen, Denmark), 2009, Vol 10, Issue 8, p1047
- ISSN
1600-0854
- Publication type
Journal Article
- DOI
10.1111/j.1600-0854.2009.00921.x