Alternative signaling: cardiomyocyte B1-adrenergic receptors signal through EGFRs

Classical ligand-activated βARs enhance cardiac contractility by coupling to Gs, formation of cAMP by adenylyl cyclase (AC), and PKA-dependent phosphorylation of various target proteins (e.g., ryanodine receptor [RyR]; phospholamban [PLN], troponin I [TnI], and the L-type Ca2+ channel [LTCC]). Chronic β1AR stimulation is detrimental and induces cardiomyocyte hypertrophy and apoptosis. In this issue of the JCI, Noma et al. () have delineated a novel signaling pathway leading to GRK- and β-arrestin–dependent Src-kinase (SRC) and MMP activation. MMP activation in turn sheds HB-EGF from the cell surface, and this serves as a ligand for cardiomyocyte EGFRs, which mediate ERK/MAPK activation. This pathway protects from β1AR-induced cardiomyocyte apoptosis but has been associated with cardiac hypertrophy.
Alternative signaling: cardiomyocyte B1-adrenergic receptors signal through EGFRs
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Publication

Alternative signaling: cardiomyocyte β1-adrenergic receptors signal through EGFRs . (2007) Stefan Engelhardt. J Clin Invest. 2007 Sep 4;117(9):2396-2398. Figure: F1.

Gene mentions


Organism Group Word Match Source NCBI Symbol NCBI ID
Homo sapiens Primates EGFR EGFR ncbigene_symbol EGFR 1956
Homo sapiens Primates MMP MMP famplex_relations MMP1 4312
Homo sapiens Primates MMP MMP famplex_relations MMP2 4313
Homo sapiens Primates MMP MMP famplex_relations MMP3 4314
Homo sapiens Primates MMP MMP famplex_relations MMP7 4316
Homo sapiens Primates MMP MMP famplex_relations MMP8 4317
Homo sapiens Primates MMP MMP famplex_relations MMP9 4318
Homo sapiens Primates MMP MMP famplex_relations MMP10 4319
Homo sapiens Primates MMP MMP famplex_relations MMP11 4320
Homo sapiens Primates MMP MMP famplex_relations MMP12 4321
Homo sapiens Primates MMP MMP famplex_relations MMP13 4322
Homo sapiens Primates MMP MMP famplex_relations MMP14 4323
Homo sapiens Primates MMP MMP famplex_relations MMP15 4324
Homo sapiens Primates MMP MMP famplex_relations MMP16 4325
Homo sapiens Primates MMP MMP famplex_relations MMP17 4326
Homo sapiens Primates MMP MMP famplex_relations MMP19 4327
Homo sapiens Primates MMP MMP famplex_relations MMP20 9313
Homo sapiens Primates MMP MMP famplex_relations MMP21 118856
Homo sapiens Primates MMP MMP famplex_relations MMP23B 8510
Homo sapiens Primates MMP MMP famplex_relations MMP24 10893
Homo sapiens Primates MMP MMP famplex_relations MMP25 64386
Homo sapiens Primates MMP MMP famplex_relations MMP26 56547
Homo sapiens Primates MMP MMP famplex_relations MMP27 64066
Homo sapiens Primates MMP MMP famplex_relations MMP28 79148
Homo sapiens Primates AC ADCY famplex_relations ADCY1 107
Homo sapiens Primates AC ADCY famplex_relations ADCY2 108
Homo sapiens Primates AC ADCY famplex_relations ADCY3 109
Homo sapiens Primates AC ADCY famplex_relations ADCY4 196883
Homo sapiens Primates AC ADCY famplex_relations ADCY5 111
Homo sapiens Primates AC ADCY famplex_relations ADCY6 112
Homo sapiens Primates AC ADCY famplex_relations ADCY7 113
Homo sapiens Primates AC ADCY famplex_relations ADCY8 114
Homo sapiens Primates AC ADCY famplex_relations ADCY9 115
Homo sapiens Primates AC ADCY famplex_relations ADCY10 55811
Homo sapiens Primates HB-EGF HBEGF ncbigene_symbol HBEGF 1839
Homo sapiens Primates SRC SRC ncbigene_symbol SRC 6714
Homo sapiens Primates SRC SRC famplex_relations FGR 2268
Homo sapiens Primates SRC SRC famplex_relations FYN 2534
Homo sapiens Primates SRC SRC famplex_relations YES1 7525
Homo sapiens Primates Ras RAS famplex_relations KRAS 3845
Homo sapiens Primates Ras RAS famplex_relations HRAS 3265
Homo sapiens Primates Ras RAS famplex_relations NRAS 4893
Homo sapiens Primates PKA PKA famplex_relations PRKAR1A 5573
Homo sapiens Primates PKA PKA famplex_relations PRKAR1B 5575
Homo sapiens Primates PKA PKA famplex_relations PRKAR2A 5576
Homo sapiens Primates PKA PKA famplex_relations PRKAR2B 5577
Homo sapiens Primates PKA PKA famplex_relations PRKACA 5566
Homo sapiens Primates PKA PKA famplex_relations PRKACB 5567
Homo sapiens Primates PKA PKA famplex_relations PRKACG 5568
Homo sapiens Primates GRK5 GRK5 ncbigene_symbol GRK5 2869
Homo sapiens Primates GRK6 GRK6 ncbigene_symbol GRK6 2870
Homo sapiens Primates Raf RAF ncbigene_synonym ZHX2 22882
Homo sapiens Primates Raf RAF famplex_relations ARAF 369
Homo sapiens Primates Raf RAF famplex_relations BRAF 673
Homo sapiens Primates Raf RAF famplex_relations RAF1 5894
Homo sapiens Primates PLN, PLN ncbigene_symbol PLN 5350
Homo sapiens Primates RyR, RYR ncbigene_synonym RYR1 6261
Homo sapiens Primates RyR, RYR ncbigene_synonym RYR2 6262
Homo sapiens Primates RyR, RYR famplex_relations RYR3 6263
Homo sapiens Primates Tnl, TNL ncbigene_synonym TRIM67 440730
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK1 5594
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK3 5595
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK11 5600
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK12 6300
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK13 5603
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK14 1432
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK8 5599
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK9 5601
Homo sapiens Primates ERK/MAPK MAPK famplex_relations MAPK10 5602
Homo sapiens Primates ERK/MAPK ERK ncbigene_synonym EPHB2 2048

Chemical mentions

Word Match MeSH Name ChEBI

Disease mentions

Word Match MeSH Name DOID
Cancer NA