The roles of Dok family adapters in immunoreceptor signaling

Immunol Rev. 2009 Nov;232(1):273-85. doi: 10.1111/j.1600-065X.2009.00844.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Lymphocyte Activation
  • MAP Kinase Kinase 4 / antagonists & inhibitors*
  • Membrane Proteins / chemistry
  • Phosphoproteins / chemistry
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / immunology
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction
  • p120 GTPase Activating Protein / metabolism


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • DOK1 protein, human
  • DOK3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • PLEKHA1 protein, human
  • Phosphoproteins
  • RNA-Binding Proteins
  • p120 GTPase Activating Protein
  • MAP Kinase Kinase 4
  • Proto-Oncogene Proteins p21(ras)