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SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase
K i Ohya1, S Kajigaya, Y Yamashita
1Division of Cardiology, Jichi Medical School, 3311-1 Yakushiji, Kawachi-gun, Tochigi 329-04, Japan.
Abstract:
Tec is the prototype of a recently emerging subfamily among nonreceptor type protein-tyrosine kinases and is known to become tyrosine-phosphorylated and activated by a wide range of cytokine stimulations in hematopoietic cells. Although Tec was recently shown to be involved in the cytokine-driven activation mechanism of c-fos transcription, it is yet obscure how Tec relays the signals from cell surface receptors to the nucleus. To identify signaling molecules acting downstream of Tec, we have looked for Tec-interacting proteins (TIPs) by using the yeast two-hybrid system. Here we report the identification and characterization of a novel protein, TIP3, which has been simultaneously identified by other groups as SOCS-1, JAB, or SSI-1. TIP3 carries one Src homology 2 domain with a sequence similarity to that of CIS. In 293 cells, TIP3 associates with Tec and suppresses its kinase activity. Interestingly, TIP3 can also down-regulate the activity of Jak2 but not that of Lyn. We propose that SOCS-1/JAB/SSI-1/TIP3 is a novel type of negative regulator to a subset of protein-tyrosine kinases.
Insights
Researchers identified TIP3, also known as SOCS-1, as a novel protein that interacts with Tec kinase. TIP3 suppresses Tec kinase activity, suggesting it acts as a negative regulator in cellular signaling pathways.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Signaling
Background:
- Tec is a key nonreceptor protein-tyrosine kinase activated by cytokines in hematopoietic cells.
- Tec's role in signal transduction from cell surface receptors to the nucleus is not fully understood.
- Identifying downstream signaling molecules of Tec is crucial for elucidating its function.
Purpose of the Study:
- To identify Tec-interacting proteins (TIPs) to understand Tec-mediated signaling.
- To characterize the novel protein TIP3 and its interaction with Tec.
- To investigate TIP3's regulatory role in protein-tyrosine kinase activity.
Main Methods:
- Yeast two-hybrid system was employed to screen for Tec-interacting proteins.
- Co-immunoprecipitation and kinase assays were used to characterize TIP3.
- Expression and functional analysis of TIP3 in 293 cells.
Main Results:
- A novel protein, TIP3 (also identified as SOCS-1, JAB, SSI-1), was identified as a Tec-interacting protein.
- TIP3 contains a Src homology 2 domain and associates with Tec in 293 cells.
- TIP3 was found to suppress the kinase activity of Tec and Jak2, but not Lyn.
Conclusions:
- TIP3 is a novel negative regulator of Tec kinase activity.
- TIP3 represents a new class of negative regulators for a subset of protein-tyrosine kinases.
- Understanding TIP3's function provides insights into cytokine signaling and hematopoietic cell regulation.