scholarly journals IGFs Potentiate TAC3-induced SLα Expression via Upregulation of TACR3 Expression in Grass Carp Pituitary Cells

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 887 ◽  
Author(s):  
Hu ◽  
He ◽  
Ko ◽  
Ye ◽  
Hu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mrna Expression ◽  
Grass Carp ◽  
Functional Expression ◽  
Mitogen Activated Protein Kinase ◽  
Hek293 Cells ◽  
Pituitary Cells ◽  
Gene Products ◽  
Receptor Signaling ◽  
Igf I

In mammals, the tachykinin 3 (TAC3)/tachykinin receptor 3 (TACR3) systems have been confirmed to play an important role in the regulation of puberty onset. Using grass carp pituitary cells as the model, our recent study found that the TAC3 gene products could significantly induce somatolactin α (SLα) synthesis and secretion via TACR3 activation. In the present study, we seek to examine if pituitary TACR3 can serve as a regulatory target and contribute to TAC3 interactions with other SLα regulators. Firstly, grass carp TACR3 was cloned and tissue distribution showed that it could be highly detected in grass carp pituitary. Using HEK293 cells as the model, functional expression also revealed that grass carp TACR3 exhibited ligand binding selectivity and post-receptor signaling highly comparable to its mammalian counterpart. Using grass carp pituitary cells as the model, TACR3 mRNA expression could be stimulated by insulin-like growth factor (IGF)-I and -II via the IGF-I receptor coupled to phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. Interestingly, IGF-I/-II cotreatment could also significantly enhance TAC3-induced SLα mRNA expression and the potentiating effect was dependent on TACR3 expression and activation of adenylate cyclase (AC)/cAMP/protein kinase A (PKA), phospholipase C (PLC)/inositol 1,4,5-triphosphate (IP3)/protein kinase C (PKC), and Ca2+/calmodulin (CaM)/calmodulin-dependent protein kinase II (CaMK-II) cascades. Besides, IGF-I-induced Akt phosphorylation but not MEK, extracellular signal-regulated kinase (ERK1/2), and P38MAPK phosphorylation was notably enhanced by TACR3 activation. These results, as a whole, suggest that the potentiating effect of IGFs on TAC3 gene products-induced SLα mRNA expression was mediated by TACR3 upregulation and functional crosstalk of post-receptor signaling in the pituitary.

scholarly journals TAC1 Gene Products Regulate Pituitary Hormone Secretion and Gene Expression in Prepubertal Grass Carp Pituitary Cells

Endocrinology ◽  
2017 ◽  
Vol 158 (6) ◽  
pp. 1776-1797 ◽  
Author(s):  
Guangfu Hu ◽  
Mulan He ◽  
Wendy K. W. Ko ◽  
Anderson O. L. Wong
Keyword(s):  
Protein Kinase ◽  
Mrna Expression ◽  
Grass Carp ◽  
Messenger Rna ◽  
Hormone Secretion ◽  
Adenosine Monophosphate ◽  
Pituitary Hormone ◽  
Neurokinin A ◽  
Pituitary Cells ◽  
Gene Products

Abstract Tachykinin-1 (TAC1) is known to have diverse functions in mammals, but similar information is scarce in fish species. Using grass carp as a model, the pituitary actions, receptor specificity and postreceptor signaling of TAC1 gene products, namely substance P (SP) and neurokinin A (NKA), were examined. TAC1 encoding SP and NKA as well as tachykinin receptors NK1R and NK2R were cloned in the carp pituitary. The newly cloned receptors were shown to be functional with properties similar to mammalian counterparts. In carp pituitary cells, SP and NKA could trigger luteinizing hormone (LH), prolactin (PRL), and somatolactin α (SLα) secretion, with parallel rises in PRL and SLα transcripts. Short-term SP treatment (3 hours) induced LH release, whereas prolonged induction (24 hours) could attenuate LHβ messenger RNA (mRNA) expression. At pituitary cell level, LH, PRL, and SLα regulation by TAC1 gene products were mediated by NK1R, NK2R, and NK3R, respectively. Apparently, SP- and NKA-induced LH and SLα secretion and transcript expression were mediated by adenylyl cyclase/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholiphase C (PLC)/inositol 1,4,5-triphosphate/protein kinase C (PKC), and Ca2+/calmodulin (CaM)/CaM-dependent protein kinase-II pathways. The signal transduction for PRL responses was similar, except for the absence of a PKC component. Regarding SP inhibition of LHβ mRNA expression, the cAMP/PKA- and PLC/PKC-dependent (but not Ca2+/CaM-dependent) cascades were involved. These results, as a whole, suggest that TAC1 gene products play a role in LH, PRL, and SLα regulation via overlapping postreceptor signaling coupled to different subtypes of tachykinin receptor expressed in the carp pituitary.

scholarly journals Novel Pituitary Actions of TAC3 Gene Products in Fish Model: Receptor Specificity and Signal Transduction for Prolactin and Somatolactin α Regulation by Neurokinin B (NKB) and NKB-Related Peptide in Carp Pituitary Cells

Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3582-3596 ◽  
Author(s):  
Guangfu Hu ◽  
Mulan He ◽  
Wendy K.W. Ko ◽  
Chengyuan Lin ◽  
Anderson O.L. Wong
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Grass Carp ◽  
Pituitary Cells ◽  
Transcript Expression ◽  
Gene Products ◽  
Neurokinin B ◽  
Related Peptide ◽  
Kinase C

Abstract TAC3 is a member of tachykinins, and its gene product neurokinin B (NKB) has recently emerged as a key regulator for LH through modulation of kisspeptin/GnRH system within the hypothalamus. In fish models, TAC3 not only encodes NKB but also a novel tachykinin-like peptide called NKB-related peptide (NKBRP), and the pituitary actions of these TAC3 gene products are still unknown. Using grass carp as a model, the direct effects and postreceptor signaling for the 2 TAC3 products were examined at the pituitary level. Grass carp TAC3 was cloned and confirmed to encode NKB and NKBRP similar to that of other fish species. In carp pituitary cells, NKB and NKBRP treatment did not affect LH release and gene expression but up-regulated prolactin (PRL) and somatolactin (SL)α secretion, protein production, and transcript expression. The stimulation by these 2 TAC3 gene products on PRL and SLα release and mRNA levels were mediated by pituitary NK2 and NK3 receptors, respectively. Apparently, NKB- and NKBRP-induced SLα secretion and transcript expression were caused by adenylate cyclase/cAMP/protein kinase A, phospholipase C/inositol 1,4,5-triphosphate/protein kinase C and Ca2+/calmodulin/Ca2+/calmodulin-dependent protein kinase II activation. The signal transduction for the corresponding responses on PRL release and mRNA expression were also similar, except that the protein kinase C component was not involved. These findings suggest that the 2 TAC3 gene products do not play a role in LH regulation at the pituitary level in carp species but may serve as novel stimulators for PRL and SLα synthesis and secretion via overlapping postreceptor signaling mechanisms coupled to NK2 and NK3 receptors, respectively.

scholarly journals IGF-I and vasoactive intestinal peptide (VIP) regulate cAMP-response element-binding protein (CREB)-dependent transcription via the mitogen-activated protein kinase (MAPK) pathway in pituitary cells: requirement of Rap1

2005 ◽  
Vol 34 (3) ◽  
pp. 699-712 ◽  
Author(s):  
M Fernández ◽  
F Sánchez-Franco ◽  
N Palacios ◽  
I Sánchez ◽  
L Cacicedo
Keyword(s):  
Protein Kinase ◽  
Vasoactive Intestinal Peptide ◽  
Mapk Pathway ◽  
Binding Protein ◽  
Mitogen Activated Protein Kinase ◽  
Pituitary Cells ◽  
Camp Response Element ◽  
Response Element ◽  
Igf I ◽  
Mitogen Activated Protein

In previous studies we demonstrated that vasoactive intestinal peptide (VIP) mediation, and interactions between mitogen-activated protein kinase (MAPK) and cAMP/protein kinase A (PKA) signaling pathways are implicated in insulin-like growth factor I (IGF-I)- and VIP-induced lactotroph proliferation. These facts led us to investigate the intracellular mechanisms involved in IGF-I- and VIP-induced lactotroph proliferation. Exposure of cultured male rat pituitary cells to IGF-I (10−7 M) or VIP (10−7 M) stimulated the MAPK cascade. Studies in GH4C1 cells, with an expression vector for Rap1 GTPase-activating protein (Rap1 GAP1), demonstrated reduced VIP-induced MAPK activation, indicating that VIP-dependent activation of the extracellular signal-regulated kinase (ERK) pathway requires PKA-Rap1 signaling. IGF-I induced cAMP-response element (CRE)-binding protein (CREB) phosphorylation through the Ras-MAPK pathway, whereas VIP phosphorylated CREB directly via PKA. The mechanisms that regulate IGF-I-and VIP-CREB-dependent gene transcription were examined using GH4C1 cells transiently transfected with a CRE reporter gene. IGF-I and VIP stimulation of CRE-mediated transcription required activation of both Ras-MAPK and cAMP/PKA signaling. This activation was blocked in the presence of Rap1 GAP1. In summary, we showed that IGF-I and VIP stimulated MAPK activity and the phosphorylation of CREB in pituitary cells. Furthermore, VIP-dependent activation of PKA-Rap1-ERK pathways mediated VIP and IGF-I effects on CREB-dependent transcription in GH4C1 cells. Thus, it is possible that VIP- and IGF-I-induced lactotroph proliferation may involve Rap1.

Somatostatin inhibits hepatic growth hormone receptor and insulin-like growth factor I mRNA expression by activating the ERK and PI3K signaling pathways

2008 ◽  
Vol 295 (2) ◽  
pp. R490-R497 ◽  
Author(s):  
Alison L. Hagemeister ◽  
Mark A. Sheridan
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Growth Hormone Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Previously, we reported that somatostatins (SS) inhibit organismal growth by reducing hepatic growth hormone (GH) sensitivity and by inhibiting insulin-like growth factor I (IGF-I) production. In this study, we used hepatocytes isolated from rainbow trout to elucidate the mechanism(s) associated with the extrapituitary growth-inhibiting actions of SS. SS-14, a predominant SS isoform, stimulated tyrosine phosphorylation of several endogenous proteins, including extracellular signal-regulated kinase (ERK), a member the mitogen-activated protein kinase (MAPK) family, and protein kinase B (Akt), a downstream target of phosphatidylinositol 3-kinase (PI3K). SS-14 specifically stimulated the phosphorylation of both ERK 1/2 and Akt in a concentration-dependent fashion. This activation occurred within 5–15 min, then subsided after 1 h. The ERK inhibitor U0126 retarded SS-14-stimulated phosphorylation of ERK 1/2, whereas the PI3K inhibitor LY294002 blocked SS-14-stimulated phosphorylation of Akt. SS-14-inhibited expression of GH receptor (GHR) mRNA was blocked by U0126 but not by LY294002. By contrast, U1026 had no effect on SS-14 inhibition of GH-stimulated IGF-I mRNA expression, whereas LY294002 partially blocked the inhibition of GH-stimulated IGF-I mRNA expression by SS-14. These results indicate that SS-14-inhibited GHR expression is mediated by the ERK signaling pathway and that the PI3K/Akt pathway mediates, at least in part, SS-14 inhibition of GH-stimulated IGF-I expression.

scholarly journals The role of mitogen-activated protein kinase–extracellular receptor kinase pathway in female fertility outcomes: a focus on pituitary gonadotropins regulation

2018 ◽  
Vol 9 (7) ◽  
pp. 209-215 ◽  
Author(s):  
Samira Kahnamouyi ◽  
Mohammad Nouri ◽  
Laya Farzadi ◽  
Masoud Darabi ◽  
Vahid Hosseini ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ovarian Function ◽  
Vascular System ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Pituitary Cells ◽  
Gonadotropin Secretion ◽  
Α Subunit ◽  
Mitogen Activated Protein ◽  
Main Components

Mammalian reproduction systems are largely regulated by the secretion of two gonadotropins, that is, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The main action of LH and FSH on the ovary is to stimulate secretion of estradiol and progesterone, which play an important role in the ovarian function and reproductive cycle control. FSH and LH secretions are strictly controlled by the gonadotropin-releasing hormone (GnRH), which is secreted from the hypothalamus into the pituitary vascular system. Maintaining normal secretion of LH and FSH is dependent on pulsatile secretion of GnRH. Extracellular signal-regulated kinase (ERK) proteins, as the main components of mitogen-activated protein kinase (MAPK) signaling pathways, are involved in the primary regulation of GnRH-stimulated transcription of the gonadotropins’ α subunit in the pituitary cells. However, GnRH-stimulated expression of the β subunit has not yet been reported. Furthermore, GnRH-mediated stimulation of ERK1 and ERK2 leads to several important events such as cell proliferation and differentiation. In this review, we briefly introduce the relationship between ERK signaling and gonadotropin secretion, and its importance in female infertility.

scholarly journals Concerted Activity of Tyrosine Phosphatase SHP-2 and Focal Adhesion Kinase in Regulation of Cell Motility

1999 ◽  
Vol 19 (4) ◽  
pp. 3125-3135 ◽  
Author(s):  
Santos Mañes ◽  
Emilia Mira ◽  
Concepción Gómez-Mouton ◽  
Zhizuang Joe Zhao ◽  
Rosa Ana Lacalle ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Cell Motility ◽  
Focal Adhesion ◽  
Tyrosine Phosphatase ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Igf I ◽  
Mitogen Activated Protein ◽  
Mcf 7

ABSTRACT The coordinated interplay of substrate adhesion and deadhesion is necessary for cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF-I) induces the adhesion of MCF-7 to vitronectin and collagen in a dose- and time-dependent manner, suggesting that IGF-I triggers the activation of different integrins. On the other hand, IGF-I promotes the association of insulin receptor substrate 1 with the focal adhesion kinase (FAK), paxillin, and the tyrosine phosphatase SHP-2, resulting in FAK and paxillin dephosphorylation. Abrogation of SHP-2 catalytic activity with a dominant-negative mutant (SHP2-C>S) abolishes IGF-I-induced FAK dephosphorylation, and cells expressing SHP2-C>S show reduced IGF-I-stimulated chemotaxis compared with either mock- or SHP-2 wild-type-transfected cells. This impairment of cell migration is recovered by reintroduction of a catalytically active SHP-2. Interestingly, SHP-2-C>S cells show a larger number of focal adhesion contacts than wild-type cells, suggesting that SHP-2 activity participates in the integrin deactivation process. Although SHP-2 regulates mitogen-activated protein kinase activity, the mitogen-activated protein kinase kinase inhibitor PD-98059 has only a marginal effect on MCF-7 cell migration. The role of SHP-2 as a general regulator of cell chemotaxis induced by other chemotactic agents and integrins is discussed.

Regulation of MAP kinase by calcium-sensing receptor in bovine parathyroid and CaR-transfected HEK293 cells

2001 ◽  
Vol 280 (2) ◽  
pp. F291-F302 ◽  
Author(s):  
Olga Kifor ◽  
R. John MacLeod ◽  
Ruben Diaz ◽  
Mei Bai ◽  
Toru Yamaguchi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Combined Treatment ◽  
Cell Types ◽  
Serine Phosphorylation ◽  
Mitogen Activated Protein Kinase ◽  
Hek293 Cells ◽  
Calcium Sensing ◽  
Cytosolic Phospholipase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Regulation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway by the extracellular calcium (Cao 2+)-sensing receptor (CaR) was investigated in bovine parathyroid and CaR-transfected human embryonic kidney (HEKCaR) cells. Elevating Cao 2+ or adding the selective CaR activator NPS R-467 elicited rapid, dose-dependent phosphorylation of ERK1/2. These phosphorylations were attenuated by pretreatment with pertussis toxin (PTX) or by treatment with the phosphotyrosine kinase (PTK) inhibitors genistein and herbimycin, the phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitor U-73122, or the protein kinase C (PKC) inhibitor GF109203X and were enhanced by the PKC activator phorbol 12-myristate 13-acetate. Combined treatment with PTX and inhibitors of both PKC and PTK nearly abolished high Cao 2+-evoked ERK1/2 activation in HEKCaR cells, demonstrating CaR-mediated coupling via both Gq and Gi. High Cao 2+ increased serine phosphorylation of the 85-kDa cytosolic phospholipase A2(cPLA2) in both parathyroid and HEKCaR cells. The selective mitogen-activated protein kinase (MAPK) inhibitor PD98059 abolished high-Cao 2+-induced ERK1/2 activation and reduced cPLA2 phosphorylation in both cell types, documenting MAPK's role in cPLA2 activation. Thus our data suggest that the CaR activates MAPK through PKC, presumably through Gq/11-mediated activation of PI-PLC, as well as through Gi- and PTK-dependent pathway(s) in bovine parathyroid and HEKCaR cells and indicate the importance of MAPK in cPLA2 activation.

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