Activation of protein kinase A induces neuronal differentiation of HiB5 hippocampal progenitor cells

Kim, Giwon; Choe, Youngshik; Park, June-Hee; Cho, Sehyung; Kim, Kyungjin

doi:10.1016/s0169-328x(02)00550-8

Cited by 51 publications

(50 citation statements)

References 35 publications

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“…Interestingly, VAChT expression is the least affected by cAMP, in contrast to our findings in the septum-derived cell line SN56, where dbcAMP treatment had a significantly greater effect on the level of VAChT mRNA than on that of ChAT (Berse and Blusztajn, 1995). Furthermore, both dbcAMP and forskolin induced distinct neurite outgrowth in NSC-19 cells, which has been reported previously in other cell lines Chijiwa et al, 1990;Gunning et al, 1981;Kao et al, 2002;Kim et al, 2002;Piiper et al, 2002).…”

Section: Effect Of Camp On Cht and Cholinergic Locus Expressionsupporting

confidence: 69%

Differential regulation of the high affinity choline transporter and the cholinergic locus by cAMP signaling pathways

Brock¹,

Nickel²,

Madziar³

et al. 2007

Brain Research

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Synthesis, storage and release of acetylcholine (ACh) require the expression of several specialized enzymes, including choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and the high-affinity choline transporter (CHT). Extracellular factors that regulate CHT expression and their signaling pathways remain poorly characterized. Using the NSC-19 cholinergic cell line, derived from embryonic spinal cord, we compared the effects of the second messenger cAMP on the expression of CHT and the cholinergic locus containing the ChAT and VAChT genes. Treatment of NSC-19 cells with dbcAMP and forskolin, thus increasing intracellular cAMP levels, significantly reduced CHT mRNA expression, while it upregulated ChAT/VAChT mRNA levels and ChAT activity. The cAMP-induced CHT downregulation was independent of PKA activity, as shown in treatments with the PKA inhibitor H-89. The alternative Epac-Rap pathway, when stimulated by a specific Epac activator, led to significant downregulation of CHT and ChAT, and, to a lesser extent, VAChT. In contrast, the PKA activator 6-BNZ-cAMP stimulated the expression of all three genes, but with varying concentration-dependence profiles. Our results indicate that elevations of intraneuronal cAMP concentration have differential effects on the cholinergic phenotype, depending on the involvement of different downstream effectors. Interestingly, although CHT is expressed predominantly in cholinergic cells, its regulation appears to be distinct from that of the cholinergic locus.

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Section: Effect Of Camp On Cht and Cholinergic Locus Expressionsupporting

confidence: 69%

Differential regulation of the high affinity choline transporter and the cholinergic locus by cAMP signaling pathways

Brock¹,

Nickel²,

Madziar³

et al. 2007

Brain Research

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“…NRP1 expression was reported to be up-regulated by cAMP/PKA pathway in olfactory neuron guidance. 48 Some other reports have shown that PKA pathway enhances differentiation of neuronal progenitor cells, 49 hippocampal progenitor cells, 50 and oligodendrocyte progenitor cells. 51 Recently, evidence is accumulating to suggest that blood vessels and nerves share a similar molecular machinery to form their networks.…”

Section: Discussionmentioning

confidence: 97%

Enhancement of vascular progenitor potential by protein kinase A through dual induction of Flk-1 and Neuropilin-1

Yamamizu

Kawasaki

Katayama

et al. 2009

Blood

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IntroductionVascular endothelial growth factor (VEGF) signaling is a key regulator of vascular development during embryogenesis as well as neovascularization in the adult. [1][2][3] Intensity of VEGF signaling is strictly controlled during vascular development through ligandreceptor interaction. 4,5 Flk1 (also designated as VEGF receptor-2) is tyrosine-phosphorylated much more efficiently than Flt1 (VEGF receptor-1) upon VEGF binding and is thought to be the major receptor in endothelial cells (ECs) for VEGF-induced responses. [6][7][8] Whereas Flk1-null mice die at embryonic day 8.5 (E8.5) to E9.5 with no organized blood vessels, 9 Flt1-null mice die at midgestation with vascular overgrowth and disorganization. 10,11 Flt1 tyrosine kinase-deficient homozygous mice, in which VEGF can bind to the cell-surface domain of Flt1 but cannot conduct kinase signaling, developed normal vessels and survived, 12 indicating that VEGF signal intensity on Flk1 is regulated by absorption of VEGF to the higher affinity receptor, Flt1. VEGF-A heterozygotes die early in gestation due to failure in vascular system formation. 13 On the other hand, 2-to 3-fold overexpression of VEGF-A from its endogenous locus results in aberrant heart development and lethality at E12.5 to E14, 14 indicating that strictly balanced VEGF function is important in normal embryogenesis.Neuropilin-1 (NRP1) is a type 1 membrane protein, which is expressed in particular classes of developing neurons 15,16 and functions as a receptor for the class 3 semaphorins mediating semaphorin-elicited inhibitory axon guidance signals to neurons. 17,18 NRP1 is also expressed in ECs of blood vessels and endocardial cells of the heart. 15,16,19 NRP1, together with Flk1, forms a specific receptor for VEGF 165 , an isoform of VEGF, and the Flk1-VEGF 165 -NRP1 complex potently enhances Flk1 signaling. 20 Coexpression of NRP1 with Flk1 in cultured ECs enhanced VEGF 165 binding to Flk1 and VEGF-elicited mitogenic and chemotactic activities. 20 Overexpression of NRP1 in mouse embryos resulted in an excess production of blood vessels and malformed hearts. 15 NRP1-null mice die midway through gestation at E10.5 to E12.5 and exhibit defects in the heart, vasculature, and nervous system. 16 These findings indicate that NRP1 plays an important role in regulating vascular development, and Flk1/NRP1 system would be important for controlling VEGF signal intensity. However, the regulatory mechanisms of Flk1/NRP1 expression in vascular development are not fully elucidated.In the early embryo and in differentiating embryonic stem (ES) cells, Flk1 expression marks a common progenitor for both blood and endothelium. [21][22][23][24] To elucidate the mechanisms underlying vascular development, we have developed a novel ES cell differentiation system that exhibits early vascular development using Flk1 ϩ cells as common progenitors for vascular cells. 25 ES cell-derived Flk1 ϩ cells can differentiate into both ECs and mural cells (MCs: vascular smooth muscle cells and pericytes) and form mature...

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“…Functionally, loss of PRKAR1A is associated with excess PKA signaling in tumors from patients (4), although the exact mechanism by which this aberrant signaling causes tissue-specific tumorigenesis is unknown. This question is particularly intriguing because activation of PKA has been shown to promote differentiation and block proliferation in many tissue culture systems (6)(7)(8)(9), and PKA agonists have recently been proposed as useful agents for chemotherapy in leukemias (10). Because of the potential for unexpected effects of such a therapy, a thorough understanding of the consequences of PKA dysregulation is therefore critical.…”

Section: Introductionmentioning

confidence: 99%

A Mouse Model for the Carney Complex Tumor Syndrome Develops Neoplasia in Cyclic AMP–Responsive Tissues

et al. 2005

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Carney complex is an autosomal dominant neoplasia syndrome characterized by spotty skin pigmentation, myxomatosis, endocrine tumors, and schwannomas. This condition may be caused by inactivating mutations in PRKAR1A, the gene encoding the type 1A regulatory subunit of protein kinase A. To better understand the mechanism by which PRKAR1A mutations cause disease, we have developed conventional and conditional null alleles for Prkar1a in the mouse. Prkar1a +/À mice developed nonpigmented schwannomas and fibro-osseous bone lesions beginning at f6 months of age. Although genotype-specific cardiac and adrenal lesions were not seen, benign and malignant thyroid neoplasias were observed in older mice. This spectrum of tumors overlaps that seen in Carney complex patients, confirming the validity of this mouse model. Genetic analysis indicated that allelic loss occurred in a subset of tumor cells, suggesting that complete loss of Prkar1a plays a key role in tumorigenesis. Similarly, tissue-specific ablation of Prkar1a from a subset of facial neural crest cells caused the formation of schwannomas with divergent differentiation. These observations confirm the identity of PRKAR1A as a tumor suppressor gene with specific importance to cyclic AMP-responsive tissues and suggest that these mice may be valuable tools not only for understanding endocrine tumorigenesis but also for understanding inherited predispositions for schwannoma formation. (Cancer Res 2005; 65(11): 4506-14)

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Activation of protein kinase A induces neuronal differentiation of HiB5 hippocampal progenitor cells

Cited by 51 publications

References 35 publications

Differential regulation of the high affinity choline transporter and the cholinergic locus by cAMP signaling pathways

Differential regulation of the high affinity choline transporter and the cholinergic locus by cAMP signaling pathways

Enhancement of vascular progenitor potential by protein kinase A through dual induction of Flk-1 and Neuropilin-1

A Mouse Model for the Carney Complex Tumor Syndrome Develops Neoplasia in Cyclic AMP–Responsive Tissues

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