2009
DOI: 10.1074/jbc.m809038200
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Abstract: Proline-rich tyrosine kinase 2 (PYK2) is a cytoplasmic, nonreceptor tyrosine kinase implicated in multiple signaling pathways. It is a negative regulator of osteogenesis and considered a viable drug target for osteoporosis treatment. The high-resolution structures of the human PYK2 kinase domain with different inhibitor complexes establish the conventional bilobal kinase architecture and show the conformational variability of the DFG loop. The basis for the lack of selectivity for the classical kinase inhibito… Show more

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Cited by 94 publications
(76 citation statements)
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“…2). The involvement of Pyk2 in the K ϩ -induced contractile response was supported by the inhibitory effect of PF-431396, a Pyk2/FAK inhibitor (13). Following sustained K ϩ -induced contraction, PF-431396 induced a concentration-dependent relaxation with an IC 50 of 0.3 Ϯ 0.1 M (Fig.…”
Section: Resultsmentioning
confidence: 78%
See 1 more Smart Citation
“…2). The involvement of Pyk2 in the K ϩ -induced contractile response was supported by the inhibitory effect of PF-431396, a Pyk2/FAK inhibitor (13). Following sustained K ϩ -induced contraction, PF-431396 induced a concentration-dependent relaxation with an IC 50 of 0.3 Ϯ 0.1 M (Fig.…”
Section: Resultsmentioning
confidence: 78%
“…9), suggesting an off-target effect of this compound during the phasic contraction. A likely target is MLCK itself because skeletal muscle MLCK has been shown to be partially inhibited by PF-431396 (13).…”
Section: Discussionmentioning
confidence: 99%
“…Deletion of the Pyk2 gene in mice leads to an increase in bone mass that is due to defects in the activity of both OBs (7) and osteoclasts (11). OBs differentiated from Pyk2 KO mice exhibit an increase in alkaline phosphatase activity and OB mineralization (7), although selective Pyk2 chemical inhibitors block Pyk2 auto-phosphorylation and increase osteogenic markers in OB-like cells (52). In addition, osteogenesis is increased in mice with OB-targeted deletion of the Pyk2 homolog FAK (53).…”
Section: Discussionmentioning
confidence: 99%
“…BMDCs were incubated for 24 h with the specified concentrations of the Pyk2/FAK-specific inhibitor (Synkinase, Melbourne, Australia) (19,20). Migration was then evaluated.…”
Section: Methodsmentioning
confidence: 99%