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Several PDE4‐family enzymes differentially regulate EPAC1‐mediated actions during VEC tubule formation
Author(s) -
Kaczmarek Milosz,
Brzezinska Paulina B,
Umana Maria B,
Maurice Donald H
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.651.3
Subject(s) - phosphodiesterase , angiogenesis , microbiology and biotechnology , matrigel , chemistry , pi3k/akt/mtor pathway , adhesion , phosphodiesterase 3 , camp dependent pathway , tubule , mapk/erk pathway , enzyme , biology , signal transduction , biochemistry , cancer research , endocrinology , protein kinase a , kidney , organic chemistry
Studies have established that several angiogenesis‐related actions of vascular endothelial cells (VECs) are differentially affected by cAMP‐elevating agents. This selectivity is coordinated, in part, by actions of cAMP at individual VEC cAMP‐signaling complexes. Indeed, recently we showed that EPAC1‐integration into a phosphodiesterase 3B (PDE3B)‐based VEC cAMP‐signalosome allows PDE3 inhibitors to activate PI3Kã and promote VEC adhesion to matrigel, an early event in tubules formation. Since EPAC1 integrates into a PDE4D‐containing, VE‐cadherin‐based, cAMP signalosomes that allows EPAC1 to control VEC intercellular contacts, but not adhesions, we investigated how PDE4 inhibitors impacted VEC tubule formation. Our findings identify distinct roles for each PDE4B and PDE4D in the control of EPAC1‐mediated effects in tubule formation and identify potential novel therapeutic strategies to control these angiogenesis‐related events.