A bombesin receptor subtype-3 peptide increases nuclear oncogene expression in a MEK-1 dependent manner in human lung cancer cells

Weber, H. Christian; Walters, James W.; Leyton, Julius; Casibang, Marchessini; Purdom, Sally; Jensen, Robert T.; Coy, David H.; Ellis, Chad A.; Clark, Geoffrey J.; Moody, Terry W.

doi:10.1016/s0014-2999(00)00941-9

Cited by 30 publications

(22 citation statements)

References 33 publications

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“…1). These studies were performed in two well-characterized cell lines that overexpress functional hBRS-3 (Fathi et al 1993;Mantey et al 1997), one of which, the mouse fibroblasts BALB3T3, does not possess any other Bn receptors, whereas in contrast the human lung cancer cells NCI-H1299 also express at low level GRP-R and NMB-R (Mantey et al 1997;Weber et al 2001). Our results showed that stimulation with hBRS-3 peptide agonists 3513, 697, and 3209 expectedly resulted in rapid, transient calcium mobilization in both cell lines.…”

Section: Discussionmentioning

confidence: 99%

A Selective Human Bombesin Receptor Subtype-3 Peptide Agonist Mediates CREB Phosphorylation and Transactivation

Qin

Coy

et al. 2011

J Mol Neurosci

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The native ligand for the G protein-coupled bombesin receptor subtype-3 (BRS-3) has currently not been identified. Studies in mice showed robust BRS-3 expression in the hypothalamic satiety centers, and genetic receptor inactivation resulted in obesity, diabetes, and hypertension. BRS-3 was also detected in normal human pancreatic islet cells suggesting a critical role of BRS-3 in regulating energy metabolism and satiety via central and peripheral mechanisms of action. The cyclic AMP response element binding protein (CREB) is a main regulator of pancreatic β-cell gene expression required for glucose homeostasis and islet cell survival, and hypothalamic regulation of satiety. Therefore, in this study we examined whether agonist-dependent hBRS-3 stimulation mediates CREB activation. A selective hBRS-3 peptide agonist and two non-selective hBRS-3 peptide agonists were used to activate ectopically expressed hBRS-3. Stimulation with hBRS-3 peptide agonists resulted in transient calcium mobilization, whereby the selective peptide agonist acted exclusively via hBRS-3 but not through the gastrin-releasing peptide receptor (GRP-R). A selective high-affinity GRP-R antagonist did not inhibit hBRS-3-mediated calcium signals. We also found time-dependent CREB phosphorylation in response to the selective hBRS-3 activation, which was abrogated by pretreatment with protein kinase A and protein kinase C inhibitors. Human BRS-3 agonists also stimulated CREB transactivation and resulted in modest increases of CRE-dependent gene transcription. These changes were significantly reduced after pretreatment with inhibitors of PKA, PKC, and MEK-1. Thus, our results suggest that hBRS-3 agonist-dependent signaling mediates CREB phosphorylation and transactivation through partially PKA, PKC, and MEK-1 pathways.

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Section: Discussionmentioning

confidence: 99%

A Selective Human Bombesin Receptor Subtype-3 Peptide Agonist Mediates CREB Phosphorylation and Transactivation

Qin

Coy

et al. 2011

J Mol Neurosci

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“…Studies in rats, mice, and monkeys indicate that the BRS-3 is expressed in the testis, the CNS, and the enteric nervous system (Fathi et al, 1993;Ohki-Hamazaki et al, 1997;Sano et al, 2004), although its physiological role remains unclear and no naturally occurring ligand has been identified . As with NMBR and GRPR, BRS-3 signaling may involve the activation of PLC, PKC, MAPK, and phospholipases (Fathi et al, 1993;Ryan et al, 1998;Weber et al, 2001;Sano et al, 2004). No involvement of BRS-3 in memory has been demonstrated to date; hence, in the next sections, we will focus on the NMBR and GRPR types of bombesin receptors.…”

Section: Brs-3 Receptor (Bb3)mentioning

confidence: 99%

Bombesin receptor regulation of emotional memory

Roesler

Kent²,

Schröder³

et al. 2012

Reviews in the Neurosciences

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Mammalian bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide (GRP) act by activating NMB receptors (NMBR, BBl) and GRP receptors (GRPR,BB2), respectively. These two bombesin receptors are members of the G-protein-coupled receptor (GPCR) superfamily.In the brain, NMBR and GRPR are highly expressed in the brain areas involved in memory processing and emotional responses, such as the hippocampus and the amygdaloid nuclei. An increasing number of pharmacological and genetic studies in rodents indicate that NMBRs and GRPRs in brain regions including the dorsal hippocampus,the nucleus tractus solitarius, the basolateral amygdala,and cortical areas, regulate memory formation and expression, particularly for memories related to emotionally arousing tasks. GRPR signaling interacts with multiple protein kinase pathways as well as with other neurotransmitter,hormone, and growth factor systems in influencing memory formation. Together with evidence from human studies, the findings from rodent experiments suggest that bombesin receptors may be therapeutic targets in brain disorders involving memory dysfunction and anxiety.

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“…BB 3 receptor stimulation also results in activation of tyrosine kinases (Ryan et al, 1998a;Weber et al, 2001), stimulating tyrosine phosphorylation of p125 FAK by a mechanism that is not dependent on either limb of the phospholipase C cascade (i.e., activation of PKC or mobilization of cellular calcium) (Ryan et al, 1998a). Activation of BB 3 receptor also stimulates MAP kinase activation, resulting in rapid tyrosine phosphorylation of both 42-and 44-kDa forms, which is inhibited by the MEK-1 inhibitor PD98059 ]bombesin 6 -14 resulted in stimulation of Elk-1 in a MEK-1-dependent manner as well as a 47-fold increase in c-fos mRNA ).…”

mentioning

confidence: 99%

International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States

Jensen

Battey

Spindel³

et al. 2007

Pharmacol Rev

469

720

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A bombesin receptor subtype-3 peptide increases nuclear oncogene expression in a MEK-1 dependent manner in human lung cancer cells

Cited by 30 publications

References 33 publications

A Selective Human Bombesin Receptor Subtype-3 Peptide Agonist Mediates CREB Phosphorylation and Transactivation

A Selective Human Bombesin Receptor Subtype-3 Peptide Agonist Mediates CREB Phosphorylation and Transactivation

Bombesin receptor regulation of emotional memory

International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States

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