The regulation of tyrosine kinase signalling pathways by growth factor and G-protein-coupled receptors

Malarkey, Kevin; Belham, Christopher; Paul, Andrew; Graham, Anne; McLees, Angela; Scott, Pamela Sharkey; Plevin, Robin

doi:10.1042/bj3090361

Cited by 264 publications

(167 citation statements)

References 251 publications

(228 reference statements)

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“…Immunodepletion of lysates with anti-SHP-2 completely blocks JAK2 association with the GST-AT 1 -(306 -359) fusion protein. 2 In the present study, we have tested whether quantitative depletion of SHP-2 from VSMC lysates also alters PLC␥1 binding to the GST-AT 1 -(306 -359) fusion protein. Lysates were prepared from Ang II-treated (10 Ϫ7 M for 30 s) VSMC and then depleted of SHP-2 by immunoprecipitation with anti-SHP-2 antibody.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, however, we have found that JAK2 associates with the receptor as a consequence of the SH2 domain-containing SHP-2 phosphotyrosine phosphatase acting as an adaptor or linker protein for JAK2 association. 2 In the present study, we have examined whether Ang II-induced tyrosine phosphorylation and activation of PLC␥1 in VSMC involves binding of PLC␥1 to the AT 1 receptor in an Ang II-and tyrosine phosphorylation-dependent manner. In addition, we have identified the interacting domains in the two proteins.…”

mentioning

confidence: 99%

“…Typically, these proteins contain one or more domains known as Src homology 2 (SH2) 1 domains. Among these SH2 domain-containing proteins are phosphoinositide-specific phospholipase C␥ (PLC␥), the 85-kDa subunit of phosphatidylinositol 3-kinase, GTPase-activating proteins, growth factor receptor binding protein 2, the phosphotyrosine phosphatase SHP-2, and members of the nonreceptor Src family of tyrosine kinases (1,2). Autophosphorylation of growth factor receptors occurs on defined tyrosine residues.…”

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confidence: 99%

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Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Venema

et al. 1998

Journal of Biological Chemistry

101

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An early event in signaling by the G-protein-coupled angiotensin II (Ang II) AT 1 receptor in vascular smooth muscle cells is the tyrosine phosphorylation and activation of phospholipase C␥1 (PLC␥1). In the present study, we show that stimulation of this event by Ang II in vascular smooth muscle cells is accompanied by binding of PLC␥1 to the AT 1 receptor in an Ang II-and tyrosine phophorylation-dependent manner. The PLC␥1-AT 1 receptor interaction appears to depend on phosphorylation of tyrosine 319 in a YIPP motif in the C-terminal intracellular domain of the AT 1 receptor and binding of the phosphorylated receptor by the most C-terminal of two Src homology 2 domains in PLC␥1. PLC␥1 thus binds to the same site in the receptor previously identified for binding by the SHP-2 phosphotyrosine phosphatase⅐JAK2 tyrosine kinase complex. A single site in the C-terminal tail of the AT 1 receptor can, therefore, be bound in a ligand-dependent manner by two different downstream effector proteins. These data demonstrate that G-protein-coupled receptors can physically associate with intracellular proteins other than G proteins, creating membrane-delimited signal transduction complexes similar to those observed for classic growth factor receptors.Growth factor receptors belong to a family of receptors that contain an extracellular ligand binding domain, a single transmembrane portion, and a large intracellular tyrosine kinase catalytic domain. Ligand-induced receptor autophosphorylation promotes the interaction of the intracellular domains of the receptors with a number of downstream effector proteins or enzymes. Typically, these proteins contain one or more domains known as Src homology 2 (SH2) 1 domains. Among these SH2 domain-containing proteins are phosphoinositide-specific phospholipase C␥ (PLC␥), the 85-kDa subunit of phosphatidylinositol 3-kinase, GTPase-activating proteins, growth factor receptor binding protein 2, the phosphotyrosine phosphatase SHP-2, and members of the nonreceptor Src family of tyrosine kinases (1, 2). Autophosphorylation of growth factor receptors occurs on defined tyrosine residues. These phosphorylated residues function to initiate cellular signaling cascades by acting as high affinity binding sites for the SH2 domains of various effector proteins. The selectivity of the receptor-effector interaction is determined, not only by the phosphorylated tyrosine residue in the receptor but also by the three amino acids Cterminal to the phosphorylated tyrosine and by the structure of the SH2 domain of the interacting protein. For example, one of the identified sites for binding of the SH2 domains of PLC␥1 to the platelet-derived growth factor ␣ and ␤ receptors is a YIPP motif present in the receptors at residues 1018 -1021 and 1021-1024, respectively. Phosphorylation of tyrosines 1018 and 1021 in these motifs promotes binding of PLC␥1 to the platelet-derived growth factor receptor and tyrosine phosphorylation and activation of the enzyme (3, 4).Another family of cell surface receptors are the G-protein...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Venema

et al. 1998

Journal of Biological Chemistry

101

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“…With respect to colon carcinogenesis, as modeled in rat colonic epithelial cells, we propose that overexpressed PKCe acts as an oncogene by providing a sustained stimulatory signal to Raf-1, bypassing the ®ne regulatory circuitry normally controlled by growth factors, growth factor receptors, adaptor molecules, GTPase-activating proteins, and other elements (Malarkey et al, 1995).…”

Section: Pkce Reverses the Inhibition Of Cell Growth Caused By Dominamentioning

confidence: 99%

“…In particular, although it has been shown that p21ras can recruit Raf-1 kinase to the plasma membrane, this interaction is not su cient for complete Raf-1 activation, which occurs via phosphorylation of speci®c serine residues by a Raf kinase-kinase (Daum et al, 1994). Several reports have suggested that PKCe and PKCa are likely candidates for this kinase in mammalian cells (reviewed in: Perletti and Monti, 1996;Daum et al, 1994;Malarkey et al, 1995). We, therefore, focused new experiments on the role of PKCe in ras signal transduction, at the level of Raf-1 activation.…”

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Protein kinase Cε is oncogenic in colon epithelial cells by interaction with the ras signal transduction pathway

et al. 1998

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We have shown previously that overexpression of the e isoform of protein kinase C (PKCe) in rat colonic epithelial cells causes malignant transformation, possibly by interacting with the ras signal transduction pathway (Oncogene 12: 847, 1996). We have now performed experiments to examine certain early steps in the ras signaling pathway. A marked increase of Raf-1 phosphorylation was detected in tumorigenic ras-transformed D/ras as well as in D/e cells (overexpressing PKCe), compared to the nontumorigenic D/WT parental line. Moreover, in the PKCe-transformed D/e cell line, stable transfection with a dominant-negative raf-1 (DNraf) sequence caused complete regression of the neoplastic phenotype. These results suggested that PKCe-induced transformation was associated with increased Raf-1 activation, and that DNraf could block the oncogenic e ect of PKCe. Furthermore, transfection of D/WT cells with dominant-negative ras induced arrest of cell growth, and subsequent transfection with PKCe cDNA enhanced cell proliferation and induced neoplastic transformation. These results suggest that ras acts upstream of PKCe, and that overexpression of PKCe circumvents the block in cell proliferation caused by dominant-negative ras. We conclude that PKCe exerts its oncogenic activity in rat colonic cells by a ecting the ras signaling cascade at the level of Raf-1 activation.Keywords: PKCe; Raf-1; colon cancer; oncogeneWe have demonstrated that the epsilon isoform of protein kinase C (PKCe) is oncogenic when overexpressed in rat colonic epithelial cells . In the previous report, we analysed the expression of several PKC isoforms in a nontumorigenic rat colonic epithelial cell line FRC/TEX CLD (D/WT), and in a derivative tumorigenic Ha-rastransformed FRC/TEX CLD/H-ras line (D/ras) (Pories et al., 1993). PKCe was markedly increased in D/ras cells when compared to the non-neoplastic D/ WT line. To assess whether overexpression of PKCe was involved in the transformed phenotype, we stably transfected D/WT cells with a PKCe cDNA construct. Overexpression of PKCe induced complete in vitro and in vivo neoplastic transformation.Because PKCe expression was found to be altered in D/ras cells, our ®ndings suggested that PKCe might exert its oncogenic activity by interacting with the ras signal transduction pathway. In particular, although it has been shown that p21ras can recruit Raf-1 kinase to the plasma membrane, this interaction is not su cient for complete Raf-1 activation, which occurs via phosphorylation of speci®c serine residues by a Raf kinase-kinase (Daum et al., 1994). Several reports have suggested that PKCe and PKCa are likely candidates for this kinase in mammalian cells (reviewed in: Perletti and Monti, 1996;Daum et al., 1994;Malarkey et al., 1995). We, therefore, focused new experiments on the role of PKCe in ras signal transduction, at the level of Raf-1 activation.Based on the ®ndings described above, we hypothesize that PKCe interacts with the ras signaling pathway, likely by activating Raf-1. Raf-1 phosphorylation is in...

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Molecular mechanisms in intimal hyperplasia

2000

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Intimal hyperplasia is the process by which the cell population increases within the innermost layer of the arterial wall, such as occurs physiologically during closure of the ductus arteriosus and during involution of the uterus. It also occurs pathologically in pulmonary hypertension, atherosclerosis, after angioplasty, in transplanted organs, and in vein grafts. The underlying causes of intimal hyperplasia are migration and proliferation of vascular smooth muscle cells provoked by injury, inflammation, and stretch. This review discusses, at a molecular level, both the final common pathways leading to smooth muscle migration and proliferation and their (patho)‐physiological triggers. It emphasizes the key roles played by growth factors and extracellular matrix‐degrading metalloproteinases, which act in concert to remodel the extracellular matrix and permit cell migration and proliferation. Copyright © 2000 John Wiley & Sons, Ltd.

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The regulation of tyrosine kinase signalling pathways by growth factor and G-protein-coupled receptors

Cited by 264 publications

References 251 publications

Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Protein kinase Cε is oncogenic in colon epithelial cells by interaction with the ras signal transduction pathway

Molecular mechanisms in intimal hyperplasia

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