Table 1. Platelet Rho GTPase effectors.
A list of known effector proteins for RhoA, Rac1 and Cdc42 compiled from Bishop and Hall [113] and Bustelo et al. [144] and cross-referenced against mRNA transcripts from human platelets [35], and two recent proteomic databases such that only proteins known to be expressed are listed [145,146].
| Effector | Protein type (alternate protein name) | Upstream GTPase | Main biological function |
|---|---|---|---|
| FilaminA | Actin binding protein | RhoA, Rac1, Cdc42 | Cytoskeletal regulation, actin filament cross-linking |
| CopG2 | Coatomer protein (γ2-Cop) | Cdc42 | Vesicle trafficking (clathrin route) |
| DIAPH1,2 | Formin | RhoA, Rac1 | Cytoskeletal change via profilin and IRSp53 |
| FHOD1 | Formin | Rac1 | Cytoskeletal and transcriptional regulation |
| FMNL1 | Formin | Rac1 | Cytoskeletal organization, cell polarity, cytokinesis |
| IP3R1 | Inositol 1,4,5-triphosphate receptor | RhoA | Calcium entry in endothelial cells |
| PI4,5PK | Lipid kinase | RhoA | Phosphatidylinositol bisphosphate level modulation |
| CybA | NADPH oxidase complex subunit | Rac1 | Superoxide production |
| NCF1,2 | NADPH oxidase complex subunit | Rac1, Cdc42 | Superoxide production |
| PLC-β2 | Phospholipase, C type (PLC-β2) | Cdc42, Rac1 | Production of second messengers |
| KCNA2 | Potassium Channel subunit | RhoA | Potassium entry |
| PIK3R1 | Regulatory p85 subunit of PIK3C | Rac1, Cdc42 | Regulation of PIK3C activity, signal transduction |
| PPP1R12A | Regulatory subunit of phosphatase1 | RhoA | MLC inactivation, cytoskeletal regulation |
| IQGAP1,2 | RhoGAP and scaffold protein | Rac1, Cdc42 | Cytoskeletal regulation, cell–cell contacts |
| ARFIP2 | Scaffold protein (Por1) | Rac1 | Cytoskeletal regulation |
| Cdc42SE1,2 | Scaffold protein (Spec1,2) | Rac1, Cdc42 | Modulation of GTPase signalling outputs |
| CYFIP1,2 | Scaffold protein (Pir121) | Rac1 | Regulation of the cytoskeleton via WASF proteins |
| MTSS1 | Scaffold protein | Rac1 | Cytoskeletal organization via WASF/WAVE |
| Kinectin1 | Scaffold protein | RhoA, Rac1, Cdc42 | Kinesin binding, microtubule vesicular trafficking |
| NCK1 | Scaffold protein with SH2/3 domains | Rac1 | Complex formation with WASP, signal transduction |
| NCKAP1 | Scaffold protein (Nap125, Nap1) | Rac1 | Regulation of the cytoskeleton via WASF proteins |
| N-WASP | Scaffold protein | Cdc42 | Cytoskeletal regulation via Arp2/3 complex |
| Pard6 A,G | Scaffold protein (Par6α,γ) | Rac1, Cdc42 | Cell polarity. Links GTPases and atypical PKCs |
| Trip10 | Scaffold protein | Cdc42 | Binding of WASP to microtubules |
| WASP | Scaffold protein | Rac1 | Cytoskeletal regulation via the Arp2/3 complex |
| WAVE/Scar1,2 | Scaffold protein | Cdc42, Rac1 | Cytoskeletal regulation via the Arp2/3 complex |
| Cdc42bpgB | Serine/threonine kinase (MRCKβ) | Rac1, Cdc42 | Cytoskeletal regulation |
| p70S6K | Serine/threonine kinase | Cdc42 | Regulation of translation, cell cycle |
| PAK2 | Serine/threonine kinase | Rac1, Cdc42 | Cytoskeletal organization, kinase activation |
| PKCα | Serine/threonine kinase | RhoA, Rac1, Cdc42 | Signal transduction |
| PKN1,2 | Serine/threonine kinase (Prk) | RhoA | Vesicle recycling, PLD1 activation |
| ROCK1,2 | Serine/threonine kinase (Rok α,β) | RhoA | Cytoskeleton, blockage of cell contact inhibition |
| Stat3 | Transcriptional factor | Rac1, Cdc42 | Transcription |
| α-Tubulin-1C | Tubulin | Rac1 | Integral component of microtubules |