RhoB regulation pathway
Ras homolog gene family, member A ( RhoB ) is a member of a family of small GTPases. Rho GTPases control multiple cellular processes, including actin and microtubule dynamics, gene expression, the cell cycle, cell polarity and membrane transport through their ability to bind to numerous downstream effectors that lead to diverse parallel downstream signaling pathways 7749321 , .
There are several classes of regulatory proteins that affect the activation state of RhoB. Guanine nucleotide exchange factors (GEFs) promote exchange of GTP for GDP, thereby activate Rho proteins. Rho/rac guanine nucleotide exchange factor (GEF) 2 ( ARHGEF2 ) and Rho guanine nucleotide exchange factor (GEF) 3 ( ARHGEF3 ) are known GEFs for RhoB , . Vav 2 guanine nucleotide exchange factor ( VAV-2 ) and Rho guanine nucleotide exchange factor (GEF) 10-like ( GrinchGEF ) also can stimulate activity of RhoB , .
Geranylgeranyltransferase type I ( GGTase-I ) and Farnesyltransferase CAAX box ( FTase ) promote post-translational modification of RhoB protein by geranylgeranylation and farnesylation. It is also essential for RhoB biological activity , .
Guaninenucleotide-dissociation inhibitors (GDIs) bind to prenylated GDP-bound Rho proteins and allow translocation between membranes and the cytosol . The most known RhoB GDIs are Rho GDP dissociation inhibitors (GDI) alpha and gamma ( RhoGDI alpha and RhoGDI gamma ). They bind to RhoB and suppress its activation , .
Once activated, the GTPases bind to a spectrum of effectors to stimulate downstream signaling pathways. RhoB binding to key effectors Diaphanous homolog 1, 3 ( DIA1, mDIA2(DIAPH3) ) and Rhophilin Rho GTPase binding protein 2 ( Rhophilin 2 ) leads to actin polymerization and cytoskeleton rearrangements and also regulates endosomal trafficking , , . Protein kinase N1 ( PRK1 ) and Rhotekin are also well-known RhoB downstream effectors , . And finally, RhoB can directly bind to Phospholipase C epsilon 1 ( PLC-epsilon 1 ) and stimulate its enzymatic activity , .