vasodilator-stimulated phosphoprotein (VASP, ENAH)

Function

• actin-associated protein involved in a range of processes dependent on cytoskeleton remodeling & cell polarity including axon guidance & lamellipodial & filopodial dynamics in migrating cells
• promotes actin nucleation & increases the rate of actin polymerization in the presence of capping protein
• associated with actin/integrin focal contacts
• major substrate for cAMP-dependent protein kinase (PKA) & cGMP-dependent protein kinase (PKG) in platelets
• preferred site for PKA is Ser-157
• preferred site for PKG, Ser-239
• in ADP-activated platelets, phosphorylation by PKA or PKG on Ser-157 leads to fibrinogen receptor inhibition
• phosphorylation on Thr-278 requires prior phosphorylation on Ser-157 & Ser-239
• in response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA
• in response to thrombin, phosphorylated by both PKC & ROCK1
• interacts with PFN1, PFN2, LPP, ACTN1 & ACTG1
• interacts, via the EVH1, with the Pro-rich regions of ZYX; this interaction is important for targeting to focal adhesions & formation of actin-rich structures at the apical surface of cells
• interacts with APBB1IP
• interacts, via Pro-rich domain, with C-terminal SH3 domain of DNMBP

Structure

• homotetramer
• the EVH2 domain is comprised of 3 regions
• block A is a thymosin-like domain required for G-actin binding; the KLKR motif within this block is essential for the G-actin binding & for actin polymerization
• block B is required for F-actin binding & subcellular location, & block C for tetramerization
• the WH1 domain mediates interaction with XIRP1
• belongs to the Ena/VASP family
• contains 1 WH1 domain

Compartment

• cytoplasm, cytoskeleton
• cell junction, focal adhesion
• cell projection, lamellipodium membrane
• cell projection, filopodium membrane
• targeted to stress fibers & focal adhesions through interaction with a number of proteins including MRL family members
• localizes to the plasma membrane in protruding lamellipodia & filopodial tips
• stimulation by thrombin or PMA, also translocates VASP to focal adhesions

Expression

highly expressed in platelets

Pathology

• role in actin-based activity of Listeria monocytogenes in platelets (putative)
• VASP interacts, via EVH1 domain, with the Pro-rich domain of Listeria monocytogenes actA

More general terms

• cytoskeletal protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7408
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7408
• OMIM: https://mirror.omim.org/entry/601703
• UniProt: http://www.uniprot.org/uniprot/P50552.html