Pyk2 can functionally compensate for loss of FAK during angiogenesis. (A and B) Knockdown of FAK (but not Pyk2) slowed the rate of sprouting in WT aortic explants, indicating FAK plays the primary role during angiogenesis in normal blood vessels. For i-EC-FAK-KO, knockdown of Pyk2 (but not FAK) inhibited the angiogenic response. Broken lines indicate sprout length. Bar, 0.25 mm. (C) Sprouting of WT aortic explants was dose-dependently blocked by either a pharmacological inhibitor selective for FAK (PF-228) or a dual FAK/Pyk2 inhibitor (PF-271). Only the dual FAK/Pyk2 inhibitor (PF-271) blocked sprouting in i-EC-FAK-KO explants. n = 6 each; *, P < 0.05 versus control shRNA or vehicle. Graphs show mean ± SEM. (D) Our results suggest a necessity for FAK and/or Pyk2 expression in ECs that can preserve the angiogenic response in i-EC-FAK-KO mice.