Cell-penetrating peptide (CPP) intracellular delivery of receptor signaling motifs provides an opportunity to regulate specific receptor @entity669 kinase signal transductions. We targeted @entity669 residues Y740 and Y751 of the @entity3820 ( @entity3820 ) and Y1175 of the @entity319 ( @entity319 ). The Y740 and Y751 motifs activated @entity22166 and @entity584 , while the Y1175 motif activated @entity22166 . Targeting either Y740 or Y751 of the @entity3820 in @entity1 pulmonary artery smooth muscle cells (HPASMC) effectively inhibited PDGF activation of @entity22166 or @entity584 . Interfering with the Y751 region of the @entity3820 proved more effective than targeting the Y740 region. The phosphorylation of Y751 of the CPP and the length and exact sequence of the mimicking peptide proved crucial. On the other hand, in @entity1 pulmonary artery endothelial cell phosphorylation of the @entity319 Y1175 CPP was not a determinant in blockage of @entity22166 activation. Likewise, the length of the peptide mimic was not crucial with a very small sequence containing the Y1175 remaining effective. Physiologic proof of concept for the effectiveness of the CPP was confirmed by blockage of HPASMC migration in response to PDGF following culture injury. Thus targeted blockage of @entity669 kinase receptor signaling can be very effective.

Targeting Receptor @entity669 Kinases and Their Downstream Signaling with Cell-Penetrating Peptides in XXXX Pulmonary Artery Smooth Muscle and Endothelial Cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity22166 :: ('2048', 'Gene') :: ['ERK'] @entity319 :: ('3791', 'Gene') :: ['VEGF receptor 2', 'VEGFR2'] @entity3820 :: ('5159', 'Gene') :: ['PDGF receptor b', 'PDGFRb'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine']
@entity1 :: (9606,Species) :: ['Human']
