Aldosterone-stimulated PKC signalling cascades: from receptor to effector

2007 ◽  
Vol 35 (5) ◽  
pp. 1049-1051 ◽  
Author(s):  
W. Thomas ◽  
V. McEneaney ◽  
B.J. Harvey
Keyword(s):  
Protein Kinase ◽  
Growth Factor Receptor ◽  
Transcriptional Response ◽  
Protein Kinase D ◽  
Cell Trafficking ◽  
Signalling Cascades ◽  
Transcriptional Changes ◽  
Epidermal Growth ◽  
Protein Kinase Signalling ◽  
Regulation Of Blood Pressure

Aldosterone plays an important role in the regulation of blood pressure. The effects of this hormone have classically been described in terms of the transcriptional regulation of genes that facilitate electrolyte transport, particularly across high-resistance epithelia. The protein kinase signalling cascades that are rapidly activated in response to aldosterone are emerging as important modulators of the transcriptional response, and may serve to prime cells for the subsequent transcriptional changes. The activation of protein kinase D through an epidermal growth factor receptor transactivation pathway by aldosterone in renal cells has the potential to impact on cell trafficking events that regulate transporter activity.

scholarly journals Follicle-Stimulating Hormone Induces Multiple Signaling Cascades: Evidence that Activation of Rous Sarcoma Oncogene, RAS, and the Epidermal Growth Factor Receptor Are Critical for Granulosa Cell Differentiation

2007 ◽  
Vol 21 (8) ◽  
pp. 1940-1957 ◽  
Author(s):  
Chad M. Wayne ◽  
Heng-Yu Fan ◽  
Xiaodong Cheng ◽  
JoAnne S. Richards
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Cell Differentiation ◽  
Growth Factor ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Granulosa Cell ◽  
Growth Factor Receptor ◽  
Signaling Cascades ◽  
Rous Sarcoma ◽  
Epidermal Growth

Abstract FSH regulates ovarian granulosa cell differentiation not only by activating adenylyl cyclase and protein kinase A (PKA) but also by other complex mechanisms. Using primary rat granulosa cell cultures, we provide novel evidence that FSH rapidly activates two small GTP-binding proteins RAP1 and RAS. FSH activation of RAP1 requires cAMP-mediated activation of exchange factor activated by cAMP/RAPGEF3 whereas FSH activation of RAS and downstream signaling cascades involves multiple factors. Specifically, FSH activation of RAS required Rous sarcoma oncogene (SRC) family tyrosine kinase (SFK) and epidermal growth factor receptor (EGFR) tyrosine kinase activities but not PKA. FSH-induced phosphorylation of ERK1/2 was blocked by dominant-negative RAS as well as by inhibitors of EGFR tyrosine kinase, metalloproteinases involved in growth factor shedding, and SFKs. In contrast, FSH-induced phosphorylation of protein kinase B (PKB/AKT) and the Forkhead transcription factor, FOXO1a occurred by SFK-dependent but RAS-independent mechanisms. The SFKs, c-SRC and FYN, and the SRC-related tyrosine kinase ABL were present and phosphorylated rapidly in response to FSH. Lastly, the EGF-like factor amphiregulin (AREG) activated RAS and ERK1/2 phosphorylation in granulosa cells by mechanisms that were selectively blocked by an EGFR antagonist but not by an SFK antagonist. However, AREG-mediated phosphorylation of PKB and FOXO1a required both EGFR and SFK activation. Moreover, we show that FSH induces AREG and that activation of the EGFR impacts granulosa cell differentiation and the expression of genes characteristic of the luteal cell phenotype. Thus, FSH orchestrates the coordinate activation of three diverse membrane-associated signaling cascades (adenylyl cyclase, RAS, and SFKs) that converge downstream to activate specific kinases (PKA, ERK1/2, and PKB/FOXO1a) that control granulosa cell function and differentiation.

Sign in / Sign up

Export Citation Format

Share Document