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. 2012 Jul 13;7(7):e38530. doi: 10.1371/journal.pone.0038530

Table 1. EPO/EPOR-modulated signal transduction factors.

gene symbol, name and Entrez ID EPO modulation (fold change) array/RTPCR known /novel EPO target Description references
Pik3cb, phosphatidylinositol 3-kinase catalytic beta subunit [74769] 2.6× up N p110beta catalytic subunit of PI3K (18594509); (19815050)
Mobkl1a, MOB1, Mps One Binder kinase activator-like 1A [68473] 2.2× up N NDR kinase regulator (20624913); (18328708)
Prkcq, protein kinase C-theta [18761] 2.3× up N PKC theta S/T kinase (20592275); (12670396)
Gnb2l1, G protein, beta polypeptide 2 like 1 [14694] 3.0× up N G-protein beta 2-like-1 (anchor for PKC) (19767770); (20093473)
Gab2, growth factor receptor bound protein 2-associated protein 2 [14389] 2.7× up N Grb2 and SHP2 docking protein (14662016); (20161778); (17374739)
Irs2, insulin receptor substrate 2 [384783] 7.4× up K insulin and IL4PY- regulated docking protein (19109238); (12506011)
Erbb2ip, Erbb2 interacting protein [59079] 3.1× down N Erbin, RTK and TGF-R modulator (17591701); (20887249)
Tirap, TIR domain-containing adaptor protein [117149] 2.4× up N IL1 and Toll receptor adaptor (12447442); (19898489)
Gnl3, guanine nucleotide binding protein-like 3 (nucleolar) [30877] 2.3× up N nuclear receptor negative co-regulator (20703089); (17623774)
Pnrc1, proline-rich nuclear receptor coactivator 1 [108767] 2.3× up N nuclear receptor positive co-regulator (10894149); (20023006)
Nol8, nucleolar protein 8 [70930] 3.1× up N GTP binding protein – binding protein (15132771); (14660641)
Plek2, plecstrin 2 [27260] 3.9× up N Pleckstrin2, PIP-regulated cytoskeletal factor (17658464); (17008542)

Twelve additional signal transduction factors (STFs) were defined as significantly EPO/EPOR- modulated targets: two are kinases, as PI3K p110beta and PKC theta; others include Rack1/Gnb2l1, Erbin/Erbb2ip (an RTK modulator), two docking proteins (Gab2, Irs2), and Pleckstrin2. References are cited by PMID number.

Among twelve remaining EPO/EPOR modulated STF's (Table 1, including references as PMID's), one has been reported previously as insulin receptor substrate-2 (Irs2), a docking protein also utilized by the IL4R. Eleven represent novel EPO- response factors. One similarly is a docking protein, Gab2, while two are kinases as PI3K's catalytic beta subunit (Pik3cb), and PKC-theta (Prkcq) (an NFKb regulator). Another, MOB1 (Mobkl1a) is a preferred substrate of Mst1/2 Ste20- like kinases. Three are G- (or G-like) proteins (or binding proteins) as Gnb2l1, Gnl3 and Nol8; and three are regulating co-factors for RTKs, Toll receptors, and nuclear receptors as Erbin/Erbb2ip, Tirap, and Pnrc1, respectively. Finally, one EPO/EPOR response factor is a regulator of cytoskeleton restructuring as Pleckstrin-2 (Plek2) (3.9-fold induction). Thus, EPO also modulates the expression of intriguingly diverse sub-sets of novel STF's with functions that will be of significant interest to further delineate (and network).