Disease relevance of ARHGAP8

• Surprisingly, ARHGAP8 expression was up-regulated in the majority of primary colorectal tumors analyzed [1].

High impact information on ARHGAP8

• BPGAP1 interacts with cortactin and facilitates its translocation to cell periphery for enhanced cell migration [2].
• Progressive deletion studies confirmed that cortactin interacted directly and constitutively with the proline-rich motif 182-PPPRPPLP-189 of BPGAP1 via its Src homology 3 domain [2].
• Our findings provide evidence that cell morphology changes and migration are coordinated via multiple domains in BPGAP1 and present a novel mode of regulation for cell dynamics by a RhoGAP protein [3].
• Fluorescence studies of epitope-tagged BPGAP1 revealed that it induced pseudopodia and increased migration of MCF7 cells [3].
• Overexpression of EEN or BPGAP1 alone induced EGF-stimulated receptor endocytosis and ERK1/2 phosphorylation [4].

Biological context of ARHGAP8

• The open reading frame encodes a peptide of 387 amino acids with high homology to human ARHGAP8 in its N-terminal domain [5].
• Herein, we describe the identification, characterization and mutational analysis of a novel RHOGAP designated as ARHGAP8, which is located within a critical region of loss-of-heterozygosity on chromosome 22q13.31 in breast and colorectal carcinomas [1].
• To further elucidate the molecular mechanism underlying cell dynamics control by BPGAP1, we used protein precipitations and matrix-assisted laser desorption/ionization mass spectrometry and identified cortactin, a cortical actin binding protein as a novel partner of BPGAP1 both in vitro and in vivo [2].
• Pull-down and co-immunoprecipitation studies with deletion mutants confirmed that EEN interacted directly with BPGAP1 via its Src homology 3 (SH3) domain binding to the proline-rich region 182-PPPRPPLP-189 of BPGAP1, with prolines 184 and 186 being indispensable for this interaction [4].
• The 23 kb genomic Arhgap8 sequence consists of eight exons and seven introns [5].

Anatomical context of ARHGAP8

• Three alternatively spliced ARHGAP8 transcripts were expressed in normal mammary gland and colon, which differed in the size of the BCH/Sec14p-like domain only [1].

Associations of ARHGAP8 with chemical compounds

• These processes were further enhanced when EEN was present together with the wildtype but not with the non-interactive proline mutant of BPGAP1 [4].

Regulatory relationships of ARHGAP8

• Filling the GAPs in cell dynamics control: BPGAP1 promotes cortactin translocation to the cell periphery for enhanced cell migration [6].

Other interactions of ARHGAP8

• Consequently, this BPGAP1 mutant failed to facilitate translocation of cortactin to the periphery, and no enhanced cell migration was observed [2].

References