The VASP-Spred-Sprouty domain puzzle.
Sprouty-related proteins with an EVH1 domain (Spreds) belong to a new protein family harboring a conserved N-terminal EVH1 domain, which is related to the VASP (vasodilator-stimulated phosphoprotein) EVH1 domain (Enabled/VASP homology 1 domain) and a C-terminal Sprouty-related domain, typical for Sprouty proteins. Spreds were, like Sproutys, initially discovered as inhibitors of the Ras/MAPK pathway, and the SPR (Sprouty-related) domains of both protein families seem to be very important for many protein interactions and cellular processes. VASP was initially characterized as a proline-rich substrate of protein kinases A and G in human platelets and later shown to be a scaffold protein, regulating both signal transduction pathways and the actin filament system. The VASP-EVH1 domain is known to bind specifically to a FP(4) binding motif, which is, for example, present in the focal adhesion proteins vinculin and zyxin. In this review we give a structural and functional overview on these three protein families and ask whether nature plays a modular protein domain puzzle with stable exchangeable elements or if these closely related domains have various functions when pasted in a different protein context.
Bundschu
Karin
K
Abteilung Biochemie und Molekulare Biologie, Universität Ulm, 89081 Ulm, Germany. karin.bundschu@gmx.de
Walter
Ulrich
U
Schuh
Kai
K
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D001792:Blood Platelets / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000502:physiology*; D008840:Microfilament Proteins / Q000502:physiology*; D008954:Models, Biological; D010750:Phosphoproteins / Q000502:physiology*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D016596:Vinculin / Q000737:chemistry; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C504812:SPRED1 protein, human; C486055:SPRY1 protein, human; C092842:ZYX protein, human; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein; D016596:Vinculin