The biological functions of A-kinase anchor proteins1 1Edited by P. E. Wright

Feliciello, Antonio; Gottesman, Max E.; Avvedimento, Enrico V.

doi:10.1006/jmbi.2001.4585

Cited by 259 publications

(219 citation statements)

References 133 publications

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“…We suggest that PKAII, formed by RII, is an efficient activator of PI3K, which stimulates AKT. The selective activity of PKAII on PI3K may be dependent on membrane anchoring of PKAII, which has been shown to phosphorylate selectively several types of receptors (40). Our results also cast a new light on the mechanisms underlying TSH-or cAMP-dependent cell growth.…”

Section: Figmentioning

confidence: 53%

The Expression of the Thyroid-stimulating Hormone (TSH) Receptor and the cAMP-dependent Protein Kinase RII β Regulatory Subunit Confers TSH-cAMP-dependent Growth to Mouse Fibroblasts

Porcellini

Messina

Gregorio

et al. 2003

Journal of Biological Chemistry

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TSH activates its specific receptor in thyroid cells and induces cAMP, a robust stimulator of thyroid cell proliferation. Conversely, cAMP is a potent inhibitor of growth in mouse fibroblasts. To dissect the signals mediating cAMP-dependent growth, we have expressed in mouse fibroblasts the human thyrotropin receptor (TSHR) or a constitutively active mutant, under the control of the tetracyclin promoter. Both TSHR and cAMP levels were modulated by tetracyclin. In the presence of serum, activation of TSHR by TSH induced growth arrest. In the absence of serum, cells expressing TSHR stimulated with TSH, replicated their DNA, but underwent apoptosis. Co-expression of cAMP-dependent protein kinase (PKA) regulatory subunit type II (RII␤) inhibited apoptosis and stimulated the growth of cells only in the presence of TSH. Expression of RII␤-PKA, in the absence of TSHR, induced apoptosis, which was reversed by cAMP. Growth, stimulated by TSHR-RII␤-PKA in mouse fibroblasts, was also dependent on Rap1 activity, indicating cAMP-dependent growth in thyroid cells. As for the molecular mechanism underlying these effects, we found that in normal fibroblasts, TSH induced AKT and ERK1/2 only in cells expressing TSHR and RII. Similarly, activation of TSHR increased cAMP levels greatly, but was unable to stimulate CREB phosphorylation and transcription of cAMP-induced genes in the absence of RII. These data provide a simple explanation for the anti-proliferative and proliferative effects of cAMP in different cell types and indicate that RII-PKAII complements TSHR action by stably propagating robust cAMP signals in cell compartments.

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Section: Figmentioning

confidence: 53%

The Expression of the Thyroid-stimulating Hormone (TSH) Receptor and the cAMP-dependent Protein Kinase RII β Regulatory Subunit Confers TSH-cAMP-dependent Growth to Mouse Fibroblasts

Porcellini

Messina

Gregorio

et al. 2003

Journal of Biological Chemistry

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“…21 In our study, we cloned a human GKAP1 cDNA and demonstrated that GKAP1 mRNA expression was highest in the testis in normal adult tissues. GKAP1 functions as an anchoring protein for cGK-Ia and seems to be similar to AKAPs (A kinase anchoring protein), 24 which binds to cAK via its regulatory subunits. We showed previously that AKAP3 (A kinase anchoring protein 3) was a CT-like antigen.…”

Section: Discussionmentioning

confidence: 99%

Identification of CCDC62‐2 as a novel cancer/testis antigen and its immunogenicity

Domae

Nakamura

et al. 2009

Intl Journal of Cancer

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Cancer/testis (CT) antigens are expressed in normal germ line tissues and various cancers. They are considered promising target molecules for immunotherapy for patients with various cancers. To identify CT antigens, we performed serological identification of antigens by recombinant expression cloning. The humoral immune response of cancer patients against a newly defined antigen was analyzed. A testicular cDNA library was immunoscreened with serum obtained from a gastric adenocarcinoma patient whose primary cancer had regressed once and most liver metastasies had disappeared transiently. We isolated 55 positive cDNA clones comprising 23 different genes. They included 4 genes with testis-specific expression profiles in the Unigene database, including coiled-coil domain containing 62 (CCDC62). RT-PCR analysis showed that the expression of 2 splice variants of CCDC62 was restricted to the testis in normal adult tissues. In malignant tissues, CCDC62 variant 2 (CCDC62-2) was aberrantly expressed in a variety of cancers, including stomach cancer. A serological survey of 191 cancer patients with a range of different cancers by ELISA revealed antibodies to CCDC62-2 in 13 patients, including stomach cancer. None of the 41 healthy donor serum samples were reactive in the same test. The serum reaction against CCDC62-2 was confirmed by western blot. CCDC62-2 is a CT antigen that is immunogenic in cancer patients.

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“…The third scaffold protein that was down-regulated in our samples, gravin/AKAP250, belongs to the family of cyclic AMP-dependent kinase-anchoring proteins (AKAPs) (Feliciello et al, 2001). Gravin forms part of a scaffold coordinating the location of, at least, protein kinase A and protein kinase C (Diviani and Scott, 2001).…”

Section: Down-regulated Genesmentioning

confidence: 99%

Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array

et al. 2002

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No clear patterns in molecular changes underlying the malignant processes in lung cancer of different histological types have been found so far. To identify critical genes in lung cancer progression we compared the expression profile of cancer related genes in 14 pulmonary adenocarcinoma patients with normal lung tissue by using the cDNA array technique. Principal component analyses (PCA) and permutation test were used to detect the differentially expressed genes. The expression profiles of 10 genes were confirmed by semiquantitative real-time RT -PCR. In tumour samples, as compared to normal lung tissue, the up-regulated genes included such known tumour markers as CCNB1, PLK, tenascin, KRT8, KRT19 and TOP2A. The downregulated genes included caveolin 1 and 2, and TIMP3. We also describe, for the first time, down-regulation of the interesting SOCS2 and 3, DOC2 and gravin. We show that silencing of SOCS2 is not caused by methylation of exon 1 of the gene. In conclusion, by using the cDNA array technique we were able to reveal marked differences in the gene expression level between normal lung and tumour tissue and find possible new tumour markers for pulmonary adenocarcinoma.

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The biological functions of A-kinase anchor proteins1 1Edited by P. E. Wright

Cited by 259 publications

References 133 publications

The Expression of the Thyroid-stimulating Hormone (TSH) Receptor and the cAMP-dependent Protein Kinase RII β Regulatory Subunit Confers TSH-cAMP-dependent Growth to Mouse Fibroblasts

The Expression of the Thyroid-stimulating Hormone (TSH) Receptor and the cAMP-dependent Protein Kinase RII β Regulatory Subunit Confers TSH-cAMP-dependent Growth to Mouse Fibroblasts

Identification of CCDC62‐2 as a novel cancer/testis antigen and its immunogenicity

Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array

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