THE PROLINE-RICH FOCAL ADHESION AND MICROFILAMENT PROTEIN VASP IS A LIGAND FOR PROFILINS

Profilins are small proteins that form complexes with G-actin and phos phoinositides and are therefore considered to link the microfilament s ystem to signal transduction pathways. In addition, they bind to poly- L-proline, but the biological significance of this interaction is not yet known. The recent molecular cloning of the vasodilator-stimulated phosphoprotein (VASP), an established in vivo substrate of cAMP- and c GMP-dependent protein kinases, revealed the presence of a proline-rich domain which prompted us to investigate a possible interaction with p rofilins. VASP is a microfilament and focal adhesion associated protei n which is also concentrated in highly dynamic regions of the cell cor tex. Here, we demonstrate that VASP is a natural proline-rich profilin ligand. Human platelet VASP bound directly to purified profilins from human platelets, calf thymus and birch pollen. Moreover, VASP and a n ovel protein were specifically extracted from total cell lysates by pr ofilin affinity chromatography and subsequently eluted either with pol y-L-proline or a peptide corresponding to a proline-rich VASP motif. F inally, the subcellular distributions of VASP and profilin suggest tha t both proteins also interact within living cells. Our data support th e hypothesis that profilin and VASP act in concert to convey signal tr ansduction to actin filament formation.