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The roles of Dok family adapters in immunoreceptor signaling



The roles of Dok family adapters in immunoreceptor signaling



Immunological Reviews 232(1): 273-285



The mammalian Dok protein family has seven members (Dok-1-Dok-7). The Dok proteins share structural similarities characterized by the NH2-terminal pleckstrin homology and phosphotyrosine-binding domains followed by SH2 target motifs in the COOH-terminal moiety, indicating an adapter function. Indeed, Dok-1 was originally identified as a 62 kDa protein that binds with p120 rasGAP, a potent inhibitor of Ras, upon tyrosine phosphorylation by a variety of protein tyrosine kinases. Among the Dok family, only Dok-1, Dok-2, and Dok-3 are preferentially expressed in hematopoietic/immune cells. Dok-1 and its closest relative Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. By contrast, Dok-3 does not bind with p120 rasGAP. However, accumulating evidence has demonstrated that Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, where the interaction of Dok-3 with SHIP-1 and Grb2 appears to be important. Here, we review the physiological roles and underlying mechanisms of Dok family proteins.

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Accession: 056490355

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PMID: 19909370

DOI: 10.1111/j.1600-065X.2009.00844.x


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