Abstract
Vav proteins play roles as guanosine nucleotide exchange factors for Rho GTPases and signaling adaptors downstream of protein tyrosine kinases. The recent sequencing of the genomes of many species has revealed that this protein family originated in choanozoans, a group of unicellular organisms from which animal metazoans are believed to have originated from. Since then, the Vav family underwent expansions and reductions in its members during the evolutionary transitions that originated the agnates, chondrichthyes, some teleost fish, and some neoaves. Exotic members of the family harboring atypical structural domains can be also found in some invertebrate species. In this review, we will provide a phylogenetic perspective of the evolution of the Vav family. We will also pay attention to the structure, signaling properties, regulatory layers, and functions of Vav proteins in both invertebrate and vertebrate species.
Highlights
Guanosine nucleotide exchange factors (GEFs) are enzymes that catalyze the exchange of guanosine diphosphate (GDP) by guanosine triphosphate (GTP) in Rho proteins, thereby allowing the rapid transition of those GTPases from the inactive (GDP-bound) to the active, GTP-bound state during cell signaling
The “body plan” of these proteins shows high phylogenetic conservation, we have found events associated with the loss of specific structural domains, changes in the spatial arrangement of those domains within the overall protein, and variations in the number of Vav family members that are associated with specific evolutionary steps
Mammalian Vav family proteins contain a common structural scaffold composed of an N-terminal calponin-homology (CH) domain, an acidic (Ac) region, the catalytic DH domain, a pleckstrin-homology (PH) region, a C1 subtype zinc finger (ZF) domain, a proline rich region (PRR), and a SH3-SH2-SH3 cassette (Figure 1A)
Summary
Guanosine nucleotide exchange factors (GEFs) are enzymes that catalyze the exchange of guanosine diphosphate (GDP) by guanosine triphosphate (GTP) in Rho proteins, thereby allowing the rapid transition of those GTPases from the inactive (GDP-bound) to the active, GTP-bound state during cell signaling. Given their multidomain structure, GEFs contribute to fine-tune the activation of. They can participate in some cases in the predetermination of the effector-binding spectra of the GTPases as well as in signaling diversification events via the engagement of GTPase-independent pathways [1,2] To accommodate all these tissueand cell type-specific regulatory requirements, the Rho GEF family has become highly diversified during evolution. Information on Vav proteins not covered in this work can be found in previous review articles [4,9]
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