In response to angiotensin II, Jak2 autophosphorylates and binds the angiotensin II AT1 receptor. By studying a variety of Jak2 deletion proteins, we now show that the Jak2 protein motif 231YRFRR is required for the co-association of this kinase with the AT1 receptor. We also used a full-length Jak2 protein containing a 231FAAAA amino acid substitution. Although this protein still autophosphorylated in response to angiotensin II, it did not co-associate with the AT1 receptor. This uncoupling indicates that AT1/Jak2 co-association is not necessary for angiotensin II-induced Jak2 autophosphorylation and that Jak2 autophosphorylation per se is insufficient for AT1 receptor co-association. In response to angiotensin II, the Jak2-231FAAAA mutant will tyrosine phosphorylate Stat1. However, in the absence of AT 1/Jak2 co-association, Stat1 did not translocate into the cell nucleus and failed to mediate gene transcription. This notable result indicates that Stat1 tyrosine phosphorylation alone is insufficient for Stat1 nuclear translocation. In summary, we now show that, although Jak2-mediated tyrosine phosphorylation of Stat1 is independent of receptor co-association, Jak2-mediated recruitment of Stat1 to the AT1 receptor is critical for Stat1 nuclear translocation and subsequent gene transcription.