<i>src</i>‐related protein tyrosine kinases are physically associated with the surface antigen CD36 in human dermal microvascular endothelial cells

Bull, Helen A.; Brickell, Paul M.; Dowd, Pauline M.

doi:10.1016/0014-5793(94)00814-0

Cited by 99 publications

(73 citation statements)

References 20 publications

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“…Fyn and other Src family kinases are known to co-precipitate with CD36 in lysates from platelets and endothelial cells (14,15), but given their mutual association with lipid raft microdomains, this is not proof of their direct interaction. Indeed, a more detailed examination failed to detect direct interaction of Fyn with CD36 (16).…”

Section: Discussionmentioning

confidence: 99%

“…c-Jun NH 2 -terminal kinase-1 is also involved in the anti-motility activity of TSP1 mediated by CD36 (13). Combined with the observation that several Src family kinases co-immunoprecipitate with CD36 (14,15), these results imply that TSP1 signals through CD36 via a physical coupling to Fyn activation. However, a subsequent study concluded that Src kinases and CD36 mutually associate with lipid rafts but lack any direct binding interaction (16).…”

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confidence: 88%

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Thrombospondin-1 Inhibits Nitric Oxide Signaling via CD36 by Inhibiting Myristic Acid Uptake

Isenberg

Jia

Fukuyama

et al. 2007

Journal of Biological Chemistry

123

110

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Although CD36 is generally recognized to be an inhibitory signaling receptor for thrombospondin-1 (TSP1), the molecular mechanism for transduction of this signal remains unclear. Based on evidence that myristic acid and TSP1 each modulate endothelial cell nitric oxide signaling in a CD36-dependent manner, we examined the ability of TSP1 to modulate the fatty acid translocase activity of CD36. TSP1 and a CD36 antibody that mimics the activity of TSP1 inhibited myristate uptake. Recombinant TSP1 type 1 repeats were weakly inhibitory, but an anti-angiogenic peptide derived from this domain potently inhibited myristate uptake. This peptide also inhibited membrane translocation of the myristoylated CD36 signaling target Fyn and activation of Src family kinases. Myristate uptake stimulated cGMP synthesis via endothelial nitric-oxide synthase and soluble guanylyl cyclase. CD36 ligands blocked myristate-stimulated cGMP accumulation in proportion to their ability to inhibit myristate uptake. TSP1 also inhibited myristate-stimulated cGMP synthesis by engaging its receptor CD47. Myristate stimulated endothelial and vascular smooth muscle cell adhesion on type I collagen via the NO/cGMP pathway, and CD36 ligands that inhibit myristate uptake blocked this response. Therefore, the fatty acid translocase activity of CD36 elicits proangiogenic signaling in vascular cells, and TSP1 inhibits this response by simultaneously inhibiting fatty acid uptake via CD36 and downstream cGMP signaling via CD47. Pathological angiogenesis or the lack thereof underlies a number of major diseases (1). Proangiogenic signals from vascular endothelial growth factors (VEGF)2 and fibroblast growth factors (FGF1 and FGF2) to induce blood vessel formation are opposed by signals from endogenous angiogenesis inhibitors, including two thrombospondins (TSP1 and TSP2) and proteolytic fragments of several extracellular matrix components (2, 3). Defining the mechanism of action of these inhibitors has been complicated by the finding that vascular cells express multiple receptors for several of these molecules. In the case of TSP1, endothelial cells express at least eight receptors, and some of these elicit pro-rather than anti-angiogenic responses (4, 5). The activities of some TSP1 receptors differ between large vessel and microvascular endothelial cells, and some are regulated by specific contextual signals (4 -6). CD36, a member of the scavenger receptor B family, is a TSP1 receptor that is selectively expressed in microvascular endothelium (7,8). CD36 was initially reported to recognize CSVTCG sequences in the type 1 repeats of TSP1 (9), but further studies identified higher affinity binding to the adjacent GVQXR sequences in the second and third type 1 repeats (10, 11). CD36 binding was markedly enhanced by epimerization of the first Ile in a peptide from the second type 1 repeat 434 GDGVITRIR 442 , where I (Ile) is the D isomer (11). TSP1, recombinant type 1 repeats of TSP1, and peptide mimetics of its CD36 binding sequences inhibit FGF2-stimulated endo...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 88%

Thrombospondin-1 Inhibits Nitric Oxide Signaling via CD36 by Inhibiting Myristic Acid Uptake

Isenberg

Jia

Fukuyama

et al. 2007

Journal of Biological Chemistry

123

110

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“…TSP is a multidomain molecule that recognizes several EC surface receptors that have been coupled to tyrosine phosphorylation events, including CD36 (Bull et al, 1994), ␣ v ␤ 3 (Blystone et al, 1996), and IAP (CD47) (Gao et al, 1996). When EC lysates were immunoblotted with an anti-CD36 antibody that recognizes bovine CD36, no CD36 expression was detected.…”

Section: Discussionmentioning

confidence: 99%

“…When EC lysates were immunoblotted with an anti-CD36 antibody that recognizes bovine CD36, no CD36 expression was detected. Furthermore, the synthetic peptide CSVTCG that interacts with CD36 (Bull et al, 1994), failed to either simulate or block the TSP effect (Young, unpublished observations). That these EC do not express CD36, nor do they respond to the CSVTCG motif in TSP, implicates a CD36-independent, tyrosine phosphorylation-dependent TSP response.…”

Section: Discussionmentioning

confidence: 99%

“…Although the specific signaling pathways to which each of these receptors is coupled remain undefined, several EC receptors, including CD36 (Bull et al, 1994), ␣ v ␤ 3 (Blystone et al, 1996) and the integrin-associated protein (IAP) (Gao et al, 1996), have been coupled to tyrosine phosphorylation events. CD36 tightly associates with several src family kinases (Bull et al, 1994). Sequences within TSP that bind to the IAP receptor have been demonstrated to induce tyrosine phosphorylation of focal adhesion kinase (FAK), paxillin, and a unidentified 90-kDa protein in human melanocytes (Gao et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Thrombospondin-1 Induces Tyrosine Phosphorylation of Adherens Junction Proteins and Regulates an Endothelial Paracellular Pathway

Goldblum

Young

Wang

et al. 1999

MBoC

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Thrombospondin-1 (TSP) induces endothelial cell (EC) actin reorganization and focal adhesion disassembly and influences multiple EC functions. To determine whether TSP might regulate EC-EC interactions, we studied the effect of exogenous TSP on the movement of albumin across postconfluent EC monolayers. TSP increased transendothelial albumin flux in a dose-dependent manner at concentrations Ն1 g/ml (2.2 nM). Increases in albumin flux were observed as early as 1 h after exposure to 30 g/ml (71 nM) TSP. Inhibition of tyrosine kinases with herbimycin A or genistein protected against the TSP-induced barrier dysfunction by Ͼ80% and Ͼ50%, respectively. TSP-exposed monolayers exhibited actin reorganization and intercellular gap formation, whereas pretreatment with herbimycin A protected against this effect. Increased staining of phosphotyrosine-containing proteins was observed in plaque-like structures and at the intercellular boundaries of TSP-treated cells. In the presence of protein tyrosine phosphatase inhibition, TSP induced dose-and time-dependent increments in levels of phosphotyrosine-containing proteins; these TSP dose and time requirements were compatible with those defined for EC barrier dysfunction. Phosphoproteins that were identified include the adherens junction proteins focal adhesion kinase, paxillin, ␥-catenin, and p120 Cas . These combined data indicate that TSP can modulate endothelial barrier function, in part, through tyrosine phosphorylation of EC proteins.

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Predominant integrin ligands expressed by osteoblasts show preferential regulation in response to both cell adhesion and mechanical perturbation

Carvalho

Bumann

Schaffer

et al. 2002

J of Cellular Biochemistry

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Previous studies have demonstrated that both mechanical perturbation and cell adhesion induced the expression of osteopontin (opn) by osteoblasts (Carvalho et al. [1998] J. Cell. Biochem. 70:376-390). The present study examined if these same stimuli on osteoblasts would induce the expression of other integrin binding proteins, specifically fibronectin (fn) and bone sialoprotein (bsp). All three genes showed three- to four-fold maximal induction in response to both cell adhesion and a single 2-h period of an applied spatially uniform, dynamic biaxial strain of 1.3% at 0.25 Hz. Each gene, however, responded with a different time course of induction to mechanical strain, with bsp, fn, and opn showing their maximal response at 1, 3, and 9 h, respectively, after the perturbation period. In contrast, peak induction to cell adhesion was observed at 24 h for bsp and opn, while fn levels peaked at 8 h. Interestingly, while both opn and fn mRNA expression returned to base line after cell adhesion, bsp mRNA levels remained elevated. Examination of collagen type I and osteocalcin mRNAs showed unaltered levels of expression in response to either type of perturbation. A common feature of the signal transduction pathways, which mediate the gene expression in response to both cell adhesion and mechanical perturbation, was the activation of specific tyrosine kinases based on the ablation of the induction of these genes by the tyrosine kinase inhibitor genistein. While cycloheximide blocked the induction of all three mRNAs in response cell adhesion, it failed to block the induction of any of these genes in response to mechanical perturbation. Such results suggest that the induction of these genes after mechanical perturbation was mediated by an immediate response to signal transduction, while cell adhesion mediated effects secondary to signal transduction. Depolymerization of microfilaments with cytochalasin D had no effect on the overall expression of any of these genes in response to cell adhesion and only blocked the induction of opn expression in response to mechanical perturbation. These results suggest that cytoskeletal integrity is only selectively important in the signal transduction of certain types of stimuli and for the regulation of certain genes. In summary, both mechanical perturbation and cell adhesion stimulated the expression of integrin binding proteins. Furthermore, while there are common features in the signal transduction processes that mediate the induction of these genes in response to both stimuli, specific genes are separately regulated by precise mechanisms that are unique to both forms of stimuli.

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src‐related protein tyrosine kinases are physically associated with the surface antigen CD36 in human dermal microvascular endothelial cells

Cited by 99 publications

References 20 publications

Thrombospondin-1 Inhibits Nitric Oxide Signaling via CD36 by Inhibiting Myristic Acid Uptake

Thrombospondin-1 Inhibits Nitric Oxide Signaling via CD36 by Inhibiting Myristic Acid Uptake

Thrombospondin-1 Induces Tyrosine Phosphorylation of Adherens Junction Proteins and Regulates an Endothelial Paracellular Pathway

Predominant integrin ligands expressed by osteoblasts show preferential regulation in response to both cell adhesion and mechanical perturbation

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