Disease relevance of PLXNB1

• Here we show that semaphorin 4D (Sema4D), a protein originally shown to regulate axonal growth cone guidance in the developing central nervous system through its receptor, plexin-B1, is highly expressed in cell lines derived from head and neck squamous cell carcinomas (HNSCCs) at both the protein and message level [1].
• Ipsilateral hemiplegia caused by right internal capsule and thalamic hemorrhage: demonstration of predominant ipsilateral innervation of motor and sensory systems by MRI, MEP, and SEP [2].
• We studied pattern-shift visual (PSVEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potentials in 38 unselected patients with motor system diseases (MSD) (28 sporadic, 10 familial) [3].
• Antisera directed against SEP show similar patterns of antigen distribution in Chlamydia trachomatis and Chlamydia psittaci RB [4].
• Thirty-two sequential posterior tibial nerve somatosensory evoked potentials (PTN-SEP) were recorded in 30 neurologically impaired, ventilated, comatose patients [5].

Psychiatry related information on PLXNB1

• One of the CJD patients had a normal size SEP, and neither patient showed hyperexcitability in SEP-recovery at C-T intervals of 20-60 msec at which there was marked MEP potentiation [6].

High impact information on PLXNB1

• Recent findings shed new light on the signalling network downstream of semaphorins and plexins by demonstrating that one of the plexins, plexin-B1, possesses an intrinsic GTPase-activating protein (GAP) activity towards R-Ras [7].
• Inactivation of R-Ras by the plexin-B1 GAP domains is required for plexin-B1-mediated effects on the cytoskeleton [7].
• Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively [8].
• Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2 [9].
• Binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of ErbB-2, resulting in the phosphorylation of both plexin-B1 and ErbB-2 [9].

Biological context of PLXNB1

• In addition, we show that ligand-induced dimerization of Plexin B is sufficient to stimulate endogenous RhoA potently and to induce the reorganization of the cytoskeleton [10].
• Further screenings of cDNA libraries identified three additional sequences closely related to SEX: these were named SEP, OCT, and NOV and were located on human chromosomes 3p, 1, and 3q, respectively [11].
• We propose that Rnd1 plays an important role in the regulation of Plexin-B1 signaling, leading to Rho activation during axon guidance and cell migration [12].
• These results suggest that PDZ domain-containing RhoGEFs play a role in Sema4D-plexin-B1 mediating signal transduction [13].
• The tissue distribution analysis indicated that plexin-B1 was co-localized with KIAA0380 and LARG in various tissues [13].

Anatomical context of PLXNB1

• Moreover, overexpression of the PDZ domain of PDZ-RhoGEF but not its regulator of G protein signaling domain prevents cell rounding and neurite retraction of differentiated PC12 cells induced by activation of endogenous Plexin B1 by semaphorin 4D [10].
• Interestingly, we have recently shown that Plexin-B1 is highly expressed in endothelial cells and that its activation by Semaphorin 4D elicits a potent proangiogenic response (J. R. Basile, A. Barac, T. Zhu, K. L. Guan, and J. S. Gutkind, Cancer Res. 64:5212-5224, 2004) [14].
• Immunocytochemical analysis showed that LARG was recruited to plasma membrane by plexin-B1 [13].
• CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytes [15].
• These findings establish that Plexin-B1 is an easily accessible receptor for CD100 within the immune system [15].

Associations of PLXNB1 with chemical compounds

• Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2 [9].
• Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors [13].
• We report that the Semaphorin 4D (Sema4D) receptor Plexin-B1 directly stimulates the intrinsic guanosine triphosphatase (GTPase) activity of R-Ras, a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth [16].
• Aberrancy produced via tryptophan depletion results in a different pattern of SEP distribution [4].
• Within C. trachomatis-infected cells, ampicillin treatment leads to high levels of SEP accumulation at the periphery of aberrant RB, while in C. psittaci, treatment causes SEP to localize to distinct punctate sites within the bacteria [4].

Physical interactions of PLXNB1

• In this study, we have identified two kinds of PDZ domain-containing Rho-specific guanine nucleotide exchange factors (RhoGEFs) as proteins interacting with plexin-B1 cytoplasmic domain [13].
• 1H, 15N and 13C Resonance assignments and secondary structure determination reveal that the minimal Rac1 GTPase binding domain of plexin-B1 has a ubiquitin fold [17].

Regulatory relationships of PLXNB1

• Semaphorin 4D/plexin-B1 induces endothelial cell migration through the activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway [14].
• These findings provide evidence that Plexin-B1 promotes endothelial cell motility through RhoA and ROK by regulating the integrin-dependent signaling networks that result in the activation of PI3K and Akt [18].

Other interactions of PLXNB1

• We have also observed that the semaphorin CD100, a ligand for plexin-B1, stimulates the interaction between plexin-B1 and active Rac [19].
• Rac specifically interacts with the cytosolic domain of plexin-B1, but not with that of plexin-A3 or -C1 [19].
• Whereas c-Met, with which plexin-B1 can interact, is known to be a potent promoter of angiogenesis, the effects of semaphorin-mediated plexin activation in endothelial cells are still poorly understood [20].
• The class 4 semaphorin CD100/Sema4D, which utilizes plexin-B1 and CD72 as receptors, exerts important biological effects on a variety of cells, including the neuronal, epithelial and immune cells [21].
• The finding that nurselike cells from B-CLL patients express CD31 and plexin-B1, which deliver growth and survival signals to CD38+/CD100+ B-CLL cells, further confirms the model proposed [22].

Analytical, diagnostic and therapeutic context of PLXNB1

• ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy [8].
• Measures of wave-shape stability were computed for auditory (AEP) and somatosensory (SEP) evoked potentials, recorded from one EOG and 14 scalp leads [23].
• Evoked potential studies of the somatosensory system with standard electrical stimulation (SEP) generally fail to establish objective correlates of such sensory deficits, because electrical stimuli predominantly activate large myelinated fibers that project into the medial lemniscal system [24].
• The heptadecapeptide form the rabbit gastrin was extracted from 16 rabbit antra and purified by a combination of DEAE Sephadex, C-18 SEP PAK cartridges, fast performance liquid chromatography (FPLC) and reverse phase high pressure liquid chromatography (HPLC) steps [25].
• The results of this study are of use for discrete and continuous PTN-SEP monitoring on intensive care units and during neuroradiological interventions and neurosurgery [5].

References