Disease relevance of ARHGDIB

• The stable expression of Delta C-LyGDI induced pulmonary metastasis in 1-1ras1000 cells, whereas expression of full-length LyGDI did not induce metastasis [1].
• In the present study, cleavage of D4-GDI (Rho-GDI 2), an abundant haemopoietic-cell GDP dissociation inhibitor for the Ras-related Rho family GTPases, was demonstrated after treatment of BJAB Burkitt-like lymphoma cells with taxol or epirubicin [2].
• Use of D4 peptide in HIV inhibition [3].
• Dopamine D3 and D4 receptor gene polymorphisms and Parkinson's disease [4].
• In aldosterone-producing adenoma, the expression of D2 and D4 was especially found in nonzona fasciculata-like cells [5].
• The forced expression of RhoGDI2 caused a significant increase in gastric cancer cell invasion in vitro, and tumor growth, angiogenesis, and metastasis in vivo, whereas RhoGDI2 depletion evidenced opposite effects [6].

Psychiatry related information on ARHGDIB

• In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions [7].
• Genetic association study between pathological gambling and a functional DNA polymorphism at the D4 receptor gene [8].
• The polymorphic variations of the D4 receptor genes should be among the factors considered in the assessment of individual differences in susceptibility to disorders such as alcohol abuse or drug addiction that may be mediated through central dopaminergic systems [9].
• Linkage studies between affective disorder and dopamine D2, D3, and D4 receptor gene loci in four Japanese pedigrees [10].
• Our investigation examined polymorphisms in the dopamine D2, D3 and D4 receptor genes, plus the dopamine transporter gene in a sample consisting of 17 multiplex social phobia families [11].

High impact information on ARHGDIB

• The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation [12].
• The D4 receptor gene has high homology to the human dopamine D2 and D3 receptor genes [13].
• We have identified the two components of the stimulatory heterodimer by amino acid sequencing as a Rho GTPase and the Rho guanine nucleotide dissociation inhibitor LyGDI [14].
• There appears to be a focal abnormality of D3 and D4 messenger RNA expression in the prefrontal cortex, with down-regulation of both, consistent with prefrontal cortical hypodopaminergia in schizophrenia [15].
• Dramatic decreases of dopamine receptor transcripts were found in the prefrontal cortex, but these changes were restricted to the D3 and D4 receptors, and localized to Brodmann area 11 (orbitofrontal cortex) [15].

Chemical compound and disease context of ARHGDIB

• Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes and response to lithium prophylaxis in mood disorders [16].

Biological context of ARHGDIB

• Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity [17].
• Importantly, the identified proteins, hnRNP D0B and Rho GDI beta, which were related with the regulation of c-myc, c-fos, and c-jun, were determined by reverse transcription-polymerase chain reaction (RT-PCR) to confirm their downregulation in proteomic study [18].
• GDP dissociation inhibitor D4-GDI (Rho-GDI 2), but not the homologous rho-GDI 1, is cleaved by caspase-3 during drug-induced apoptosis [2].
• Assignment of the human GDID4 gene, a GDP/GTP-exchange regulator, to chromosome 12p12.3 [19].
• Our study does not exclude the possibility that regulatory elements of the D4 dopamine gene located elsewhere in the genome may be involved in the etiology of schizophrenia [20].

Anatomical context of ARHGDIB

• In addition, association of Rac2 and RhoGDI or LyGDI is abrogated or not detectable based on the low Rac2 expression in patients' neutrophils [21].
• In addition, we found that stimulation of U937 cells with phorbol ester leads to phosphorylation of D4/LyGDI [17].
• We have combined microanalytical liquid chromatography with the use of specific antibodies in order to separate D4/LyGDI and RhoDGI-complexes from the cytosol of U937 cells and to demonstrate that the two GDIs associate with different rho protein partners [17].
• In contrast to Rho-GDI, which is ubiquitously expressed, Ly-GDI is expressed only in hematopoietic tissues and predominantly in B- and T-lymphocyte cell lines [22].
• When hematopoietic cell lines are induced to differentiate, the expression of D4 is modulated [23].

Associations of ARHGDIB with chemical compounds

• D4 might function also as a regulator of guanine nucleotide exchange for small GTP-binding proteins [23].
• Ly-GDI is phosphorylated on tyrosine residues following T cell receptor stimulation, and it associates with the Src homology 2 region of an adapter protein, Shc [24].
• Activation of D4 receptors can increase aldosterone secretion, whereas an inhibitory effect is mediated via D2 receptors [5].
• No significant difference in the synthesis of cortisol, corticosterone, progesterone, 17-hydroxyprogesterone (17-OHP), and delta-4-androstenedione (D4) was observed between the two groups [25].
• Talipexole and the ropinirole metabolite, SKF-104557, were partial agonists at the hD4 receptor [26].

Physical interactions of ARHGDIB

• We have solved the crystal structure of a complex between the RhoGDI homolog LyGDI and GDP-bound Rac2, which are abundant in leukocytes, representing the cytosolic, resting pool of Rho species to be activated by extracellular signals [27].
• The full-length Ly-GDI cDNA encodes a 27-kDa protein which binds to RhoA and inhibits GDP dissociation from RhoA [22].

Regulatory relationships of ARHGDIB

• Our results suggest that LyGDI forms complexes with specific rho GTPases expressed in hematopoietic cells where it may regulate specific pathways [17].
• Moreover, Ly-GDI does not alter the regulation of these phenomena when coexpressed with oncogenic Vav1 [24].

Other interactions of ARHGDIB

• RhoGDI is a ubiquitously expressed GDI, whereas D4/LyGDI is hematopoietic cell-specific and 10-fold less potent than RhoGDI in binding to and regulating rho GTPases [17].
• Ly-GDI, a GDP-dissociation inhibitor of the RhoA GTP-binding protein, is expressed preferentially in lymphocytes [22].
• Here, we studied the functional significance of the interaction between Vav1 and Ly-GDI in T cells [24].
• At 8 h, intact Ly-GDI was decreased to 33% on fibronectin, compared with 69% on PolyHema (P<0.05) [28].
• TNF-alpha-mediated neutrophil apoptosis involves Ly-GDI, a Rho GTPase regulator [28].

Analytical, diagnostic and therapeutic context of ARHGDIB

• Vav1 and Ly-GDI two regulators of Rho GTPases, function cooperatively as signal transducers in T cell antigen receptor-induced pathways [24].
• The functional variants of the D4 dopamine receptor gene were identified by a combination of Southern blot techniques and the polymerase chain reaction [20].
• Northern blot analysis revealed an unexpected profile of D4 mRNA in the brain [29].
• Sequence analysis revealed that one of these proteins was Ly-GDI, a regulator of Rho GTPases [28].
• Western blot analysis revealed that platelet membranes bind anti-dopamine D3 or D5 receptor protein antibodies, but not anti-D1, D2 or D4 receptor protein antibodies [30].

References