Transmembrane-4 Superfamily Proteins Associate with Activated Protein Kinase C (PKC) and Link PKC to Specific β1 Integrins

Zhang, Xin A.; Bontrager, Alexa L.; Hemler, Martin E.

doi:10.1074/jbc.m102156200

Cited by 323 publications

(303 citation statements)

References 71 publications

(61 reference statements)

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“…Therefore, we performed the present study to clarify the signal pathway of MRP-1/CD9, which might lead to new strategies of treatment for cancer patients. MRP-1/CD9 is considered to exert its biological functions by forming a functional complex with integrin a3b1 and integrin a6b1 (Zhang et al, 2001b;GutierrezLopez et al, 2003). In fact, a previous clinical study has revealed that reduced integrin a3 expression is also a poor prognostic factors in patients with lung adenocarcinomas .…”

Section: Discussionmentioning

confidence: 99%

MRP-1/CD9 gene transduction downregulates Wnt signal pathways

et al. 2004

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Motility-related protein-1 (MRP-1/CD9) is a transmembrane glycoprotein that has been implicated in cell adhesion, motility, proliferation, and differentiation. It has a functional role as a tumor metastatic suppressor. During tumor progression, a reduction of MRP-1/CD9 gene expression results in tumor cells with a high metastatic potential. However, the mechanism of action of MRP-1/CD9 is still unclear. We studied changes of gene expression in relation to MRP-1/CD9 gene transduction into tumor cell lines, HT1080 and A549, using microarray assays and real-time PCR. Consequently, we have demonstrated that MRP-1/ CD9 gene transduction can downregulate expression of several Wnt family genes, such as Wnt1, Wnt2b1 and Wnt5a, and their target genes, including WISP-1 (Wnt-1 induced secreted protein 1), WISP-3, c-Myc, vascular endothelial growth factor-A, and matrix metalloproteinase-26. Western blot analyses also showed that MRP-1/CD9 gene transduction downregulated expression of Wnt1 protein and its target proteins. In addition, a neutralizing anti-MRP-1/CD9 monoclonal antibody inhibited the downregulation of Wnt signal pathways in MRP-1/CD9-transfected cells. The present study has revealed that the MRP-1/CD9 signal is located upstream of the Wnt signal pathways. Therefore, MRP-1/CD9 could suppress cell transformation including epithelial to mesenchymal transition through downregulation of Wnt1, and might suppress tumor metastasis through downregulation of Wnt5a.

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Section: Discussionmentioning

confidence: 99%

MRP-1/CD9 gene transduction downregulates Wnt signal pathways

et al. 2004

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“…Tetraspanins lack intrinsic activity and their effects are mediated by protein interactions. Several different proteins have been shown to associate with CD82 (Yunta and Lazo, 2003), including a3b1, a4b1, a5b1, and a6b1 integrins (Berditchevski and Odintsova, 1999;Berditchevski, 2001;Yunta and Lazo, 2003); the serine/threonine kinase PKCa (Berditchevski and Odintsova, 1999;Berditchevski, 2001;Zhang et al, 2001); B-cell receptors CD4, CD8, and CD19 (Imai et al, 1995;Mannion et al, 1996;Hammond et al, 1998); other tetraspanins including CD81, CD63, and CD9 (Vogt et al, 2002); receptor tyrosine kinases EGFR and ErbB2 (Odintsova et al, 2000(Odintsova et al, , 2003; an Ig super family molecule EW12 (Zhang et al, 2003b); and a newly identified tetraspanin molecule, kitenin, which is expressed in gastric cancers (Lee et al, 2004b).…”

Section: Introductionmentioning

confidence: 99%

Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases

2005

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KAI1/CD82, a tetraspanin protein, was first identified as a metastasis suppressor in prostate cancer. How loss of CD82 expression promotes cancer metastasis is unknown. Restoration of CD82 expression to physiological levels in the metastatic prostate cell line PC3 inhibits integrinmediated cell migration and invasion, but does not affect integrin expression. Integrin-dependent activation of the receptor kinase c-Met is dramatically reduced in CD82-expressing cells, as is c-Met activation by its ligand HGF/ SF. CD82 expression also reduced integrin-induced activation and phosphorylation of the cytoplasmic tyrosine kinase Src, and its downstream substrates p130Cas and FAK Y861. Inhibition of c-Met expression or Src kinase function reduced matrigel invasion of PC3 cells to the same extent as CD82 expression. These data indicate that CD82 functions to suppress integrin-induced invasion by regulating signaling to c-Met and Src kinases, and suggests that CD82 loss may promote metastasis by removing a negative regulator of c-Met and Src signaling.

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“…These tetraspanin complexes link extracellular interactions to the second messenger system. For example, CD81 and other tetraspanins can form a molecular complex with integrins to regulate interactions of the cell with the extracellular matrix, affecting second messenger systems (phosphatidylinositol 4-kinase) and eventually modulating the mitotic activity of the cell [1,2,20]. To date, the data indicate that CD81 is part of a molecular switch that controls reactive gliosis and the proliferation of non-neuronal elements in the retina.…”

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confidence: 99%

Temporal regulation of CD81 following retinal injury in the rat

Song

Geisert

Vázquez-Chona

et al. 2003

Neuroscience Letters

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Following retinal injury, glial cells within the retina undergo a response that is characterized by the proliferation of astrocytes, Müller cells, and retinal pigment epithelial cells. CD81, a small membrane protein known to be involved in cell proliferation, is up-regulated after injury. This study focuses on the temporal regulation of CD81, relating the expression of this protein to glial fibrillary acidic protein (GFAP), the classic marker of gliosis. CD81 levels were elevated at 7 days after injury and remained elevated at 30 days after injury; GFAP was increased at 7 days and continued to increase until 30 days post injury. This association of CD81 with glial reactivity may provide a clue to the regulation of the proliferative response following retinal injury. KeywordsCD81; Glial fibrillary acidic protein; Retina; Injury; Tetraspanin; Gliosis; ProliferationThe response of the retina to trauma involves well-characterized cellular reactions [16], many of them similar to responses that occur in other parts of the central nervous system. As in the brain and spinal cord, a dramatic up-regulation of glial fibrillary acidic protein (GFAP) follows retinal injury. This up-regulation of GFAP marks reactive retinal astrocytes [12,16], which hypertrophy and increase their expression of the intermediate filament protein GFAP [3,13,18]. Müller glia and the retinal pigment epithelium (RPE), which are unique to the retina, also demonstrate characteristic responses to injury. Müller cells, like astrocytes, up-regulate GFAP. In addition, both Müller glia cells and RPE cells can proliferate to form scar tissues within the retina [14]. They also can migrate into the vitreal space, proliferate, and form cellular membranes [7], a response known as proliferative vitreoretinopathy [11]. These cellular membranes can then contract and cause secondary retinal detachments. The reactive glial responses and the proliferation of non-neuronal cells can have serious consequences, including loss of sight.Studies in our laboratory have identified a protein, CD81, which plays a role in the response of the brain [9], spinal cord [5], and retina [10]. We originally called CD81 the target of the antiproliferative antibody. As that name implies, this protein is part of a molecular complex that controls the proliferation of glial cells. We have hypothesized that this CD81 molecular complex is a key element in the contact inhibition between glial cells in the brain. Antibodies directed against CD81 depress the mitotic activity of cultured cells [9,17]. Furthermore, CD81 is expressed by glial cells in the brain during the second postnatal week, a time when their mitotic activity is down-regulated [19]. The antiproliferative role of this protein is confirmed by mice with a CD81-null mutation [10]. These CD81-null mice have very large brains containing an over abundance of astrocytes and microglia [10]. We have found that CD81 is In this study, we used the monoclonal antibody AMP1 to recognize CD81 [9]. A polyclonal antibody purchased from Li...

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Transmembrane-4 Superfamily Proteins Associate with Activated Protein Kinase C (PKC) and Link PKC to Specific β1 Integrins

Cited by 323 publications

References 71 publications

MRP-1/CD9 gene transduction downregulates Wnt signal pathways

MRP-1/CD9 gene transduction downregulates Wnt signal pathways

Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases

Temporal regulation of CD81 following retinal injury in the rat

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