Phosphotyrosine Binding-Mediated Oligomerization of Downstream of Tyrosine Kinase (Dok)-1 and Dok-2 Is Involved in CD2-Induced Dok Phosphorylation
Bibliographic record
Abstract
To date, five members of the downstream of tyrosine kinase (Dok) family have been characterized. In T cells, two members, Dok-1 and Dok-2, are expressed. CD2 or CD28 stimulation, but not CD3/TCR stimulation, induces Dok phosphorylation. Recent evidence suggests that they act as negative regulators of the CD2 and CD28 signaling pathways. To identify the molecular mechanisms involved in Dok-mediated inhibition, we have identified proteins that bind to the phosphotyrosine-binding (PTB) domain of Dok-1 and Dok-2. We showed that the Dok PTB domain mediates phosphotyrosine-dependent homotypic and heterotypic interactions of Dok-1 and Dok-2. Moreover, in CD2-stimulated Jurkat cells, Dok-1 coimmunoprecipitates with tyrosine-phosphorylated Dok-2. To study the involvement of PTB-mediated oligomerization in Dok function, we have generated Jurkat clones overexpressing Dok-1 or Dok-2 with a mutation that prevents oligomerization (in either the PTB domain or Tyr146 of Dok-1 and Tyr139 of Dok-2). These mutations abrogate CD2-induced phosphorylation and the ability of Dok-1 or Dok-2 to inhibit CD2-induced ERK1/2 and NFAT activation. Moreover, overexpression of Dok-1Y146F or Dok-2Y139F interferes with CD2-induced phosphorylation of endogenous Dok, whereas overexpression of PTB mutant or wild-type Dok does not. Taken together, these data indicate that PTB-mediated oligomerization of Dok-1 and Dok-2 represents an essential step for Dok phosphorylation and function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".