Bombesin receptor signaling pathway module

The bombesin receptor signaling pathway (GO:0031989) is initiated when the secreted, C-terminally alpha-amidated mammalian bombesin-like neuropeptide hormones gastrin-releasing peptide (GRP, PANTHER:PTHR16866:SF2) and neuromedin B (NMB, PANTHER:PTHR16866:SF3) bind and activate their cognate seven-transmembrane G protein-coupled receptors GRPR (BB2, PANTHER:PTHR45695:SF7) and NMBR (BB1, PANTHER:PTHR45695:SF8) at the plasma membrane of central nervous system neurons, gastrointestinal endocrine/smooth-muscle cells, and anterior pituitary thyrotrophs. Agonist-bound GRPR and NMBR couple primarily to heterotrimeric Gq/11 proteins (exemplified by GNAQ, PANTHER:PTHR10218:SF329) to stimulate phospholipase C-beta (PLCB1, PANTHER:PTHR10336:SF12), generating inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) to mobilize intracellular Ca2+ and regulate gastrin secretion, smooth-muscle contraction, sighing, itch transmission, and circadian/neuroendocrine rhythms.

MODULE:bombesin_receptor_signalingDRAFTSignaling Pathwaymodules/bombesin_receptor_signaling.yaml
bombesin receptor signaling pathwayGO:0031989
GO:0031989
bombesin receptor signaling pathway
The module is grounded in the GO biological process term for the bombesin receptor signaling pathway (GO:0031989: the series of molecular signals generated as a consequence of a bombesin receptor binding to its physiological ligand).
Reactome:R-HSA-375384
Bombesin-like receptors bind bombesin homologues
Establishes that mammalian bombesin-like peptides (GRP and NMB) bind and activate GRPR and NMBR to initiate bombesin receptor signaling.
Bombesin-like receptors are widely distributed in the CNS as well as in the GI tract where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism, and behaviour through the binding of bombesin-like peptides. They include gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R) (Corjay MH et al, 1991) and bombesin-like receptor-3 (BRS-3) (Fathi Z et al, 1993).
PMID:3211139
Posttranslational processing of endogenous and of baculovirus-expressed human gastrin-releasing peptide precursor.
Demonstrates proteolytic processing and C-terminal alpha-amidation of human pro-GRP to mature bioactive GRP1-27.
In the small-cell lung cancer cell line, GRP1-27 was cleaved as expected from the endogenous prohormone at a pair of basic amino acids (29 and 30) and alpha-amidated at its C-terminal methionine
PMID:2458345
Molecular cloning of cDNAs encoding the human bombesin-like peptide neuromedin B. Chromosomal localization and comparison to cDNAs encoding its amphibian homolog ranatensin.
Establishes human NMB as a secreted bombesin-like neuropeptide precursor homologous to amphibian ranatensin and GRP.
The amidated decapeptide neuromedin B (NMB) is the mammalian homolog of the amphibian bombesin-like peptide ranatensin. cDNAs encoding human neuromedin B and amphibian ranatensin were isolated from human hypothalamic and Rana pipiens skin libraries, respectively.
PANTHER:PTN008565241
PAINT node PTN008565241 for bombesin-like peptides (PTHR16866)
Local PAINT IBD node in PTHR16866 with propagated terms C:GO:0005576, F:GO:0005184, P:GO:0007218; PAINT date 20260529.

Curated signaling-pathway module for the bombesin receptor signaling pathway (GO:0031989) built with PANTHER FAMILY/subfamily selectors across the endogenous bombesin-like peptide ligands GRP (PANTHER:PTHR16866:SF2) and NMB (PANTHER:PTHR16866:SF3), their cognate G protein-coupled receptors GRPR (PANTHER:PTHR45695:SF7) and NMBR (PANTHER:PTHR45695:SF8), and downstream Gq/11 alpha (GNAQ, PANTHER:PTHR10218:SF329) and phospholipase C-beta (PLCB1, PANTHER:PTHR10336:SF12) signaling effectors.

3Nodes
2Parts
0Variant Sets
0Variants
6Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:bombesin_receptor_signaling deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

3 gene-function check(s) reflected in core functions · 0 conflict(s) · 6 evidence or coverage gap(s) (12 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
grp_gastrin_releasing_peptide_ligand GRP
UniProtKB:P07492
Family Representative 		neuropeptide hormone activity
GO:0005184 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nmb_neuromedin_b_ligand NMB
UniProtKB:P08949
Family Representative 		neuropeptide hormone activity
GO:0005184 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
grpr_receptor GRPR
UniProtKB:P30550
Family Representative 		bombesin receptor activity
GO:0004946 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
nmbr_receptor NMBR
UniProtKB:P28336
Family Representative 		bombesin receptor activity
GO:0004946 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
gnaq_gq_alpha GNAQ
UniProtKB:P50148
Family Representative 		G protein activity
GO:0003925 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
plcb1_phospholipase_c_beta PLCB1
UniProtKB:Q9NQ66
Family Representative 		phosphatidylinositol phospholipase C activity
GO:0004435 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
grp_gastrin_releasing_peptide_ligand Gastrin-releasing peptide subfamily
PANTHER:PTHR16866:SF2
Family 		neuropeptide hormone activity
GO:0005184 		Family Supported
Family review supports GO:0005184 FAMILY_WIDE. All members of PANTHER:PTHR16866 (GRP in SF2 and NMB in SF3) function as secreted neuropeptide hormones enabling GO:0005184.
nmb_neuromedin_b_ligand Neuromedin-B subfamily
PANTHER:PTHR16866:SF3
Family 		neuropeptide hormone activity
GO:0005184 		Family Supported
Family review supports GO:0005184 FAMILY_WIDE. All members of PANTHER:PTHR16866 (GRP in SF2 and NMB in SF3) function as secreted neuropeptide hormones enabling GO:0005184.
grpr_receptor Gastrin-releasing peptide receptor subfamily
PANTHER:PTHR45695:SF7
Family 		bombesin receptor activity
GO:0004946 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR45695:SF7.
nmbr_receptor Neuromedin-B receptor subfamily
PANTHER:PTHR45695:SF8
Family 		bombesin receptor activity
GO:0004946 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR45695:SF8.
gnaq_gq_alpha Guanine nucleotide-binding protein G(q) subunit alpha subfamily
PANTHER:PTHR10218:SF329
Family 		G protein activity
GO:0003925 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR10218:SF329.
plcb1_phospholipase_c_beta 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 subfamily
PANTHER:PTHR10336:SF12
Family 		phosphatidylinositol phospholipase C activity
GO:0004435 		Family Supported
Family review supports GO:0004435 FAMILY_WIDE. Every reviewed member (fungal PLC1/plc1, PLCG1, PLCG2) accepts it. fgfr_signaling selects SF173 (PLCG1) and myo_inositol_and_inositol_phosphate_biosynthesis selects SF36 (fungal PLC).

Gene-review completeness (3/6 grounded genes reviewed)

2 complete review(s) · 0 with deep research · 3 missing review · 3 reviewed but lacking deep research

Gene Review Complete Deep research
GNAQ P50148 ✓ 111/121 ✗
GRP P07492 ✓ ✓ ✗
NMB P08949 ✓ ✓ ✗
NMBR P28336 ✗ — —
GRPR P30550 ✗ — —
PLCB1 Q9NQ66 ✗ — —

Details

Context
EuteleostomiNCBITaxon:117571
extracellular regionGO:0005576 plasma membraneGO:0005886 cytosolGO:0005829
Bombesin receptor signaling pathwaySignaling Pathwaybombesin_receptor_signaling
bombesin receptor signaling pathwayGO:0031989
Context
EuteleostomiNCBITaxon:117571
extracellular regionGO:0005576 plasma membraneGO:0005886 cytosolGO:0005829

Connections

Binding of mature alpha-amidated GRP or NMB to GRPR or NMBR stabilizes the active receptor conformation that catalyzes GDP-to-GTP exchange on GNAQ and activates PLCB1.
Part 1: bombesin-like peptide ligand-receptor engagement
GRP and NMB engagement of bombesin receptors GRPR and NMBRRegulatory Stepbombesin_receptor_engagement

Secreted C-terminally alpha-amidated gastrin-releasing peptide (GRP) and neuromedin B (NMB) bind the orthosteric pockets of their cognate seven-transmembrane bombesin receptors GRPR (BB2) and NMBR (BB1) at the plasma membrane of target neurons and endocrine/smooth-muscle cells.

Annotons

GRP gastrin-releasing peptide ligand
grp_gastrin_releasing_peptide_ligand
Participant: Family: Gastrin-releasing peptide subfamily
Family:
Gastrin-releasing peptide subfamilyPANTHER:PTHR16866:SF2
Representative Members: GRPUniProtKB:P07492

Function

neuropeptide hormone activityGO:0005184

Processes

bombesin receptor signaling pathwayGO:0031989

Locations

extracellular regionGO:0005576

Endogenous mammalian bombesin-like neuropeptide hormone that selectively binds and activates the gastrin-releasing peptide receptor (GRPR / BB2) to initiate bombesin receptor signaling.

Reactome:R-HSA-375384
Bombesin-like receptors bind bombesin homologues
Establishes GRP as an endogenous bombesin-like peptide agonist of GRPR.
Bombesin-like receptors are widely distributed in the CNS as well as in the GI tract where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism, and behaviour through the binding of bombesin-like peptides. They include gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R) (Corjay MH et al, 1991) and bombesin-like receptor-3 (BRS-3) (Fathi Z et al, 1993).
PMID:3211139
Posttranslational processing of endogenous and of baculovirus-expressed human gastrin-releasing peptide precursor.
Establishes proteolytic cleavage and C-terminal alpha-amidation of human GRP.
In the small-cell lung cancer cell line, GRP1-27 was cleaved as expected from the endogenous prohormone at a pair of basic amino acids (29 and 30) and alpha-amidated at its C-terminal methionine
NMB neuromedin-B ligand
nmb_neuromedin_b_ligand
Participant: Family: Neuromedin-B subfamily
Family:
Neuromedin-B subfamilyPANTHER:PTHR16866:SF3
Representative Members: NMBUniProtKB:P08949

Function

neuropeptide hormone activityGO:0005184

Processes

bombesin receptor signaling pathwayGO:0031989

Locations

extracellular regionGO:0005576

Endogenous mammalian ranatensin/bombesin-like neuropeptide hormone that selectively binds and activates the neuromedin-B receptor (NMBR / BB1) to initiate bombesin receptor signaling.

Reactome:R-HSA-375384
Bombesin-like receptors bind bombesin homologues
Establishes NMB as an endogenous bombesin-like peptide agonist of NMBR.
Bombesin-like receptors are widely distributed in the CNS as well as in the GI tract where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism, and behaviour through the binding of bombesin-like peptides. They include gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R) (Corjay MH et al, 1991) and bombesin-like receptor-3 (BRS-3) (Fathi Z et al, 1993).
PMID:2458345
Molecular cloning of cDNAs encoding the human bombesin-like peptide neuromedin B. Chromosomal localization and comparison to cDNAs encoding its amphibian homolog ranatensin.
Establishes human NMB as a secreted bombesin-like neuropeptide precursor.
The amidated decapeptide neuromedin B (NMB) is the mammalian homolog of the amphibian bombesin-like peptide ranatensin. cDNAs encoding human neuromedin B and amphibian ranatensin were isolated from human hypothalamic and Rana pipiens skin libraries, respectively.
GRPR gastrin-releasing peptide receptor
grpr_receptor
Participant: Family: Gastrin-releasing peptide receptor subfamily
Family:
Gastrin-releasing peptide receptor subfamilyPANTHER:PTHR45695:SF7
Representative Members: GRPRUniProtKB:P30550

Function

bombesin receptor activityGO:0004946

Processes

bombesin receptor signaling pathwayGO:0031989

Locations

plasma membraneGO:0005886

Seven-transmembrane G protein-coupled bombesin receptor (BB2) that binds GRP with high affinity and activates heterotrimeric Gq/11 signaling.

Reactome:R-HSA-375384
Bombesin-like receptors bind bombesin homologues
Establishes GRPR as a principal mammalian bombesin receptor.
They include gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R) (Corjay MH et al, 1991) and bombesin-like receptor-3 (BRS-3) (Fathi Z et al, 1993).
NMBR neuromedin-B receptor
nmbr_receptor
Participant: Family: Neuromedin-B receptor subfamily
Family:
Neuromedin-B receptor subfamilyPANTHER:PTHR45695:SF8
Representative Members: NMBRUniProtKB:P28336

Function

bombesin receptor activityGO:0004946

Processes

bombesin receptor signaling pathwayGO:0031989

Locations

plasma membraneGO:0005886

Seven-transmembrane G protein-coupled bombesin receptor (BB1) that binds NMB with high affinity and activates heterotrimeric Gq/11 signaling.

Reactome:R-HSA-375384
Bombesin-like receptors bind bombesin homologues
Establishes NMBR as a principal mammalian bombesin receptor.
They include gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R) (Corjay MH et al, 1991) and bombesin-like receptor-3 (BRS-3) (Fathi Z et al, 1993).
Part 2: Gq/11 and phospholipase C-beta effector activation
Gq/11 and phospholipase C-beta effector activation downstream of GRPR/NMBRRegulatory Stepbombesin_gq_plc_coupling

Agonist-activated GRPR and NMBR catalyze GDP-to-GTP exchange on heterotrimeric Gq/11 alpha subunits (exemplified by GNAQ), which directly stimulate plasma-membrane phospholipase C-beta (exemplified by PLCB1) to hydrolyze PIP2 into IP3 and DAG.

Annotons

GNAQ Gq alpha subunit
gnaq_gq_alpha
Participant: Family: Guanine nucleotide-binding protein G(q) subunit alpha subfamily
Family:
Guanine nucleotide-binding protein G(q) subunit alpha subfamilyPANTHER:PTHR10218:SF329
Representative Members: GNAQUniProtKB:P50148

Function

G protein activityGO:0003925

Processes

bombesin receptor signaling pathwayGO:0031989 phospholipase C-activating G protein-coupled receptor signaling pathwayGO:0007200

Locations

plasma membraneGO:0005886

Heterotrimeric Gq alpha subunit activated by ligand-bound GRPR and NMBR to stimulate phospholipase C-beta.

Reactome:R-HSA-375384
Bombesin-like receptors bind bombesin homologues
Demonstrates Gq/11 coupling downstream of bombesin-like receptors.
PLCB1 phospholipase C-beta-1 effector
plcb1_phospholipase_c_beta
Participant: Family: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 subfamily
Family:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 subfamilyPANTHER:PTHR10336:SF12
Representative Members: PLCB1UniProtKB:Q9NQ66

Function

phosphatidylinositol phospholipase C activityGO:0004435

Processes

bombesin receptor signaling pathwayGO:0031989

Locations

plasma membraneGO:0005886

Phospholipase C-beta effector activated by GTP-bound GNAQ downstream of GRPR and NMBR to generate IP3 and DAG.

Reactome:R-HSA-375384
Bombesin-like receptors bind bombesin homologues
Demonstrates PLC-beta activation in bombesin receptor signaling.