Search for directed genic interactions:  

AKT1 PIK3CA (1 - 6 of 6)
PMID: 10362672
Activation of Akt/protein kinase B after stimulation with angiotensin II in vascular smooth muscle cells.
... stimulates Akt/PKB activity ... and PI3K are required for ...   (details)

AKT1 PIK3CA

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  PI3K   (PIK3CA   PIK3R1 )

PMID: 10362672

Activation of Akt/protein kinase B after stimulation with angiotensin II in vascular smooth muscle cells.
Source

The American journal of physiology (June 1999)

Abstract

Activation of Akt/protein kinase B after stimulation with angiotensin II in vascular smooth muscle cells. Involvement of Akt/Protein kinase B (PKB), a serine/threonine kinase with a pleckstrin-homology domain, in angiotensin II (ANG II) -induced signal transduction was investigated in cultured vascular smooth muscle cells (VSMC). Stimulation of the cells with ANG II led to a marked increase in the kinase activity of Akt/PKB, which coincided with Ser-473 phosphorylation. ANG II-stimulated Akt/PKB activation was rapid, concentration dependent, and inhibited by the AT1-receptor antagonist CV-11974, but not by pertussis toxin. Akt/PKB activity was stimulated by the Ca2+ ionophore ionomycin, suggesting the possible involvement of Ca2+ in ANG II-stimulated Akt/PKB activation. However, blockade of Ca2+ mobilization by BAPTA-AM only partially inhibited ANG II-stimulated Akt/PKB activation. ANG II-stimulated Akt/PKB activation was inhibited by the tyrosine kinase inhibitors genistein and herbimycin A and by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY-294002. These results indicate that ANG II stimulates Akt/PKB activity via AT1 receptors in VSMC and that the activities of tyrosine kinase and PI3K are required for this activation.

PMID: 10444426
In vivo regulation of protein-serine kinases by insulin in skeletal muscle of fructose-hypertensive rats.
... of PI3K and ... was enhanced, ... both PKB and ...   (details)

AKT1 PIK3CA

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  PI3K   (PIK3CA   PIK3R1 )

PMID: 10444426

In vivo regulation of protein-serine kinases by insulin in skeletal muscle of fructose-hypertensive rats.
Source

The American journal of physiology (August 1999)

Abstract

In vivo regulation of protein-serine kinases by insulin in skeletal muscle of fructose-hypertensive rats. The effects of tail-vein insulin injection (2 U/kg) on the regulation of protein-serine kinases in hindlimb skeletal muscle were investigated in hyperinsulinemic hypertensive fructose-fed (FF) animals that had been fasted overnight. Basal protein kinase B (PKB) activity was elevated about twofold in FF rats and was not further stimulated by insulin. Phosphatidylinositol 3-kinase (PI3K), which lies upstream of PKB, was increased approximately 3.5-fold within 2-5 min by insulin in control rats. Basal and insulin-activated PI3K activities were further enhanced up to 2-fold and 1.3-fold, respectively, in FF rats. The 70-kDa S6 kinase (S6K) was stimulated about twofold by insulin in control rats. Both basal and insulin-stimulated S6K activity was further enhanced up to 1.5-fold and 3.5-fold, respectively, in FF rats. In control rats, insulin caused a 40-50% reduction of the phosphotransferase activity of the beta-isoform of glycogen synthase kinase 3 (GSK-3beta), which is a PKB target in vitro. Basal GSK-3beta activity was decreased by approximately 40% in FF rats and remained unchanged after insulin treatment. In summary, 1) the PI3K -- > PKB -- > S6K pathway was upregulated under basal conditions, and 2) insulin stimulation of PI3K and S6K activities was enhanced, but both PKB and GSK-3 were refractory to the effects of insulin in FF rats.

PMID: 10880354
Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155.
... and PKB does ... phosphorylation suppressed by ... of PI3K.   (details)

AKT1 PIK3CA

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  PI3K   (PIK3CA   PIK3R1 )

PMID: 10880354

Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155.
Source

The Biochemical journal (7/15/2000)

Abstract

Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155. The interaction of BAD (Bcl-2/Bcl-X (L) -antagonist, causing cell death) with Bcl-2/Bcl-X (L) is thought to neutralize the anti-apoptotic effects of the latter proteins, and may represent one of the mechanisms by which BAD promotes apoptosis. A variety of survival signals are reported to induce the phosphorylation of BAD at Ser (112) or Ser (136), triggering its dissociation from Bcl-2/Bcl-X (L). Ser (136) is thought to be phosphorylated by protein kinase B (PKB, also called Akt), which is activated when cells are exposed to agonists that stimulate phosphatidylinositol 3-kinase (PI3K). In contrast, Ser (112) is reported to be phosphorylated by mitogen-activated protein (MAP) kinase-activated protein kinase-1 (MAPKAP-K1, also called RSK) and by cAMP-dependent protein kinase (PKA). Here we identify Ser (155) as a third phosphorylation site on BAD. We find that Ser (155) is phosphorylated preferentially by PKA in vitro and is the only residue in BAD that becomes phosphorylated when cells are exposed to cAMP-elevating agents. The phosphorylation of BAD at Ser (155) prevents it from binding to Bcl-X (L) and promotes its interaction with 14-3-3 proteins. We also provide further evidence that MAPKAP-K1 mediates the phosphorylation of Ser (112) in response to agonists that activate the classical MAP kinase pathway. However insulin-like growth factor 1, a potent activator of PI3K and PKB does not increase the phosphorylation of Ser (136) in BAD-transfected HEK-293 cells, and nor is the basal level of Ser (136) phosphorylation suppressed by inhibitors of PI3K.

PMID: 12244133
Binding of protein kinase B to the plakin family member periplakin.
PI3K activation ... and PKB activation requires PtdIns3P ...   (details)

AKT1 PIK3CA

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  PI3K   (PIK3CA   PIK3R1 )

PMID: 12244133

Binding of protein kinase B to the plakin family member periplakin.
Source

Journal of cell science (10/15/2002)

Abstract

Binding of protein kinase B to the plakin family member periplakin. The serine/threonine kinase protein kinase B (PKB/c-Akt) acts downstream of the lipid kinase phosphoinositide 3-kinase (PI3K) and functions as an essential mediator in many growth-factor-induced cellular responses such as cell cycle regulation, cell survival and transcriptional regulation. PI3K activation generates 3'-phosphorylated phosphatidylinositol lipids (PtdIns3P) and PKB activation requires PtdIns3P-dependent membrane translocation and phosphorylation by upstream kinases. However PKB activation and function is also regulated by interaction with other proteins. Here we show binding of PKB to periplakin, a member of the plakin family of cytolinker proteins. Interaction between PKB and periplakin was mapped to part of the pleckstrin homology (PH) domain of PKB, which is probably not involved in lipid binding, and indeed binding to periplakin did not affect PKB activation. We therefore investigated the possibility that periplakin may act as a scaffold or localization signal for PKB. In cells endogenous periplakin localizes to different cellular compartments, including plasma membrane, intermediate filament structures, the nucleus and mitochondria. Overexpression of the C-terminal part of periplakin, encompassing the PKB binding region, results in predominant intermediate filament localization and little nuclear staining. This also resulted in inhibition of nuclear PKB signalling as indicated by inhibition of PKB-dependent Forkhead transcription factor regulation. These results suggest a possible role for periplakin as a localization signal in PKB-mediated signalling.

PMID: 12668683
Regulation of the phosphatidylinositol 3-kinase, Akt/protein kinase B, FRAP/mammalian target of rapamycin, and ribosomal S6 kinase 1 signaling pathways by thyroid-stimulating hormone (TSH) and stimulating type TSH receptor antibodies in the thyroid gland.
... and PI3K, ... might involve the ... not Akt/protein kinase B.   (details)

AKT1 PIK3CA

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

Theme:  PI3K   (PIK3CA   PIK3R1 )

PMID: 12668683

Regulation of the phosphatidylinositol 3-kinase, Akt/protein kinase B, FRAP/mammalian target of rapamycin, and ribosomal S6 kinase 1 signaling pathways by thyroid-stimulating hormone (TSH) and stimulating type TSH receptor antibodies in the thyroid gland.
Source

The Journal of biological chemistry (6/13/2003)

Abstract

Regulation of the phosphatidylinositol 3-kinase, Akt/protein kinase B, FRAP/mammalian target of rapamycin, and ribosomal S6 kinase 1 signaling pathways by thyroid-stimulating hormone (TSH) and stimulating type TSH receptor antibodies in the thyroid gland. Thyroid-stimulating hormone (TSH) regulates the growth and differentiation of thyrocytes by activating the TSH receptor (TSHR). This study investigated the roles of the phosphatidylinositol 3-kinase (PI3K), PDK1, FRAP/mammalian target of rapamycin, and ribosomal S6 kinase 1 (S6K1) signaling mechanism by which TSH and the stimulating type TSHR antibodies regulate thyrocyte proliferation and the follicle activities in vitro and in vivo. The TSHR immunoprecipitates exhibited PI3K activity, which was higher in the cells treated with either TSH or 8-bromo-cAMP. TSH and cAMP increased the tyrosine phosphorylation of TSHR and the association between TSHR and the p85alpha regulatory subunit of PI3K. TSH induced a redistribution of PDK1 from the cytoplasm to the plasma membrane in the cells in a PI3K- and protein kinase A-dependent manner. TSH induced the PDK1-dependent phosphorylation of S6K1 but did not induce Akt/protein kinase B phosphorylation. The TSH-induced S6K1 phosphorylation was inhibited by a dominant negative p85alpha regulatory subunit or by the PI3K inhibitors wortmannin and LY294002. Rapamycin inhibited the phosphorylation of S6K1 in the cells treated with either TSH or 8-bromo-cAMP. The stimulating type TSHR antibodies from patients with Graves disease also induced S6K1 activation, whereas the blocking type TSHR antibodies from patients with primary myxedema inhibited TSH- but not the insulin-induced phosphorylation of S6K1. In addition, rapamycin treatment in vivo inhibited the TSH-stimulated thyroid follicle hyperplasia and follicle activity. These findings suggest an interaction between TSHR and PI3K, which is stimulated by TSH and cAMP and might involve the downstream S6K1 but not Akt/protein kinase B. This pathway may play a role in the TSH/stimulating type TSH receptor antibody-mediated thyrocyte proliferation in vitro and in the response to TSH in vivo.

PMID: 21663621
PIK3CA-mediated PI3-kinase signalling is essential for HPV-induced transformation in vitro.
... subunit PIK3CA as ... as activation of ... effector PKB/AKT progressively ...   (details)

AKT1 PIK3CA

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 21663621

PIK3CA-mediated PI3-kinase signalling is essential for HPV-induced transformation in vitro.
Source

Molecular cancer (2011)

Abstract

PIK3CA-mediated PI3-kinase signalling is essential for HPV-induced transformation in vitro. [BACKGROUND] High-risk human papillomavirus (hrHPV) infections are causally related to cervical cancer development. The additional (epi) genetic alterations driving malignant transformation of hrHPV-infected cells however, are not yet fully elucidated. In this study we experimentally assessed the role of the PI3-kinase pathway and its regulator PIK3CA, which is frequently altered in cervical cancer, in HPV-induced transformation. [METHODS] Cervical carcinomas and ectocervical controls were assessed for PIK3CA mRNA and protein expression by quantitative RT-PCR and immunohistochemical staining, respectively. A longitudinal in vitro model system of hrHPV-transfected keratinocytes, representing the immortal and anchorage independent phenotype, was assayed for PI3-kinase activation and function using chemical pathway inhibition i.e. LY294002 treatment, and PIK3CA RNA interference. Phenotypes examined included cellular viability, migration, anchorage independent growth and differentiation. mRNA expression of hTERT and HPV16 E6E7 were studied using quantitative RT-PCR and Northern blotting. [RESULTS] Cervical carcinomas showed significant overexpression of PIK3CA compared to controls. During HPV-induced transformation in vitro, expression of the catalytic subunit PIK3CA as well as activation of downstream effector PKB/AKT progressively increased in parallel. Inhibition of PI3-kinase signalling in HPV16-transfected keratinocytes by chemical interference or siRNA-mediated silencing of PIK3CA resulted in a decreased phosphorylation of PKB/AKT. Moreover, blockage of PI3-kinase resulted in reduced cellular viability, migration, and anchorage independent growth. These properties were accompanied with a downregulation of HPV16E7 and hTERT mRNA expression. In organotypic raft cultures of HPV16- and HPV18-immortalized cells, phosphorylated PKB/AKT was primarily seen in differentiated cells staining positive for cytokeratin 10 (CK10). Upon PI3-kinase signalling inhibition, there was a severe impairment in epithelial tissue development as well as a dramatic reduction in p-PKB/AKT and CK10. [CONCLUSION] The present data indicate that activation of the PI3-kinase/PKB/AKT pathway through PIK3CA regulates various transformed phenotypes as well as growth and differentiation of HPV-immortalized cells and may therefore play a pivotal role in HPV-induced carcinogenesis.