XXXX interacts with oncogenic lymphocyte-specific protein @entity669 kinase.

@entity4635 @entity20139 @entity5 @entity10393 @entity5740 @entity19933 @entity2952 @entity669
Lymphocyte-specific protein @entity669 kinase ( @entity2952 ) plays a key role in T cell signal transduction and is tightly regulated by phosphorylation and dephosphorylation. @entity2952 can function as an oncoprotein when overexpressed or constantly activated by mutations. Our previous studies showed that @entity2952 -induced cellular transformation could be suppressed by enforced expression of @entity4635 ( @entity4635 ), a @entity19933 family member involved in the negative feedback control of cytokine signaling. We observed attenuated @entity2952 kinase activity in @entity4635 -expressing cells, suggesting an important role of @entity19933 in regulating @entity2952 functions. It remains largely unknown whether and how @entity19933 proteins interact with the oncogenic @entity2952 kinase. Here, we report that among four @entity19933 family proteins, @entity4635 , @entity20139 , @entity5740 and CIS (cytokine-inducible SH2 domain containing protein), @entity4635 has the highest affinity in binding to the oncogenic @entity2952 kinase. We identified the positive regulatory @entity10393 394 residue in the kinase domain as the key interacting determinant in @entity2952 . Additionally, the @entity2952 kinase domain alone is sufficient to bind @entity4635 . While the SH2 domain in @entity4635 is important in its association with the oncogenic @entity2952 kinase, other functional domains may also contribute to overall binding affinity. These findings provide important mechanistic insights into the role of @entity19933 proteins as @entity5 suppressors in cells transformed by oncogenic protein @entity669 kinases.
