A Mouse Model for the Study of SYK Function through Chemical Genetics Demonstrates SYK-Dependent Signaling through the B Cell Receptor, but Not TLR4.

The SYK protein-tyrosine kinase is a well-known mediator of signals elicited by the clustering of BCR complexes and other receptors that bear components that contain one or more ITAM sequences. Additional roles for the kinase in signaling through other receptor classes also have been described. To assist in the identification of SYK-regulated processes, we developed mice lacking endogenous genes but containing instead genes coding for an analogue-sensitive form of SYK (SYK-AQL).

A Computational Study of the Effects of Syk Activity on B Cell Receptor Signaling Dynamics.

The kinase Syk is intricately involved in early signaling events in B cells and is required for proper response when antigens bind to B cell receptors (BCRs). Experiments using an analog-sensitive version of Syk (Syk-AQL) have better elucidated its role, but have not completely characterized its behavior. We present a computational model for BCR signaling, using dynamical systems, which incorporates both wild-type Syk and Syk-AQL.

Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy.

Syk is a cytoplasmic kinase that serves multiple functions within the immune system to couple receptors for antigens and antigen-antibody complexes to adaptive and innate immune responses. Recent studies have identified additional roles for the kinase in cancer cells, where its expression can either promote or suppress tumor cell growth, depending on the context. Proteomic analyses of Syk-binding proteins identified several interacting partners also found to be recruited to stress granules.

Calling in SYK: SYK's dual role as a tumor promoter and tumor suppressor in cancer.

SYK (spleen tyrosine kinase) is well-characterized in the immune system as an essential enzyme required for signaling through multiple classes of immune recognition receptors. As a modulator of tumorigenesis, SYK has a bit of a schizophrenic reputation, acting in some cells as a tumor promoter and in others as a tumor suppressor. In many hematopoietic malignancies, SYK provides an important survival function and its inhibition or silencing frequently leads to apoptosis.

Nanomechanical property maps of breast cancer cells as determined by multiharmonic atomic force microscopy reveal Syk-dependent changes in microtubule stability mediated by MAP1B.

The Syk protein-tyrosine kinase, a well-characterized modulator of immune recognition receptor signaling, also plays important, but poorly characterized, roles in tumor progression, acting as an inhibitor of cellular motility and metastasis in highly invasive cancer cells. Multiharmonic atomic force microscopy (AFM) was used to map nanomechanical properties of live MDA-MB-231 breast cancer cells either lacking or expressing Syk. The expression of Syk dramatically altered the cellular topography, reduced cell height, increased elasticity, increased viscosity, and allowed visualization of a more substantial microtubule network.