SOCS-1 JAB/SSI-1 CAN BIND TO AND SUPPRESS TEC PROTEIN-TYROSINE KINASE/

Tec is the prototype of a recently emerging subfamily among nonrecepto r type protein-tyrosine kinases and is known to become tyrosine-phosph orylated and activated by a wide range of cytokine stimulations in hem atopoietic cells, Although Tec was recently shown to be involved in th e cytokine-driven activation mechanism of c-fos transcription, it is y et obscure how Tec relays the signals from cell surface receptors to t he 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 tile identification and characteriz ation of a novel protein, TIP3, which has been simultaneously identifi ed by other groups as SOCS-1, JAB, or SSI-l. TIP3 carries one Src homo logy 2 domain with a sequence similarity to that of CIS. In 293 cells, TIPB associates with Tec and suppresses its kinase activity. Interest ingly, TIPB can also down-regulate the activity of Jak2 but not that o f Lyn. We propose that SOCS-1/JAB/SSI-1/TIP3 is a novel type of negati ve regulator to a subset of protein-tyrosine kinases.