Focal Adhesion Kinase–Related Protein Tyrosine Kinase Pyk2 in T-Cell Activation and Function

Abstract

Pyk2 is a protein tyrosine kinase expressed primarily in brain and hematopoietic cells. It becomes activated in response to stimulation through numerous receptors, including integrins, chemokine receptors, and antigen receptors, and is found in association with src-family kinases. Although this enzyme associates with many proteins known to be important for activation and has many characteristics of a scaffolding protein, its function remains elusive. A number of studies in non-T-cells suggest that Pyk2 is important for cell spreading, cell migration, and integrin function; however, a defined role in T-cells has not been established. Here, we discuss evidence that implicates Pyk2 in directionality of signaling, which is essential to establishment of the directional killing mediated by cytotoxic lymphocytes.

Dectin-1 Stimulation Induces Suppressor of Cytokine Signaling 1, Thereby Modulating TLR Signaling and T Cell Responses

“…Thus, different activation patterns of Pyk2, calcium dependent (25) and independent (as concluded from our experiments) are possible. Pyk2 plays an important role in cell morphology, motility, and adhesion in a variety of cells including macrophages (24,42). Its role in inflammation is only beginning to be explored.…”

Pyk2 Inhibition of p53 as an Adaptive and Intrinsic Mechanism Facilitating Cell Proliferation and Survival

“…Proline-rich kinase-2 (Pyk2) 6 and focal adhesion kinase (FAK) 6 are related cytoplasmic protein-tyrosine kinases that contain N-terminal 4.1, ezrin, radixin, moesin (FERM), central kinase, proline-rich, and C-terminal focal adhesion targeting domains (1,2). FAK is abundant and ubiquitously expressed, whereas high level Pyk2 expression is selective and cell typespecific (3).…”

“…In fibroblasts this difference is due to FAK recruitment and activation at integrin-enriched focal adhesion sites, whereas Pyk2 remains primarily perinuclear-distributed (5). Determining the similarities and differences of FAK-Pyk2 action is an area that remains under investigation (6,7).…”

Hypertension Promotes Phosphorylation of Focal Adhesion Kinase and Proline-Rich Tyrosine Kinase 2 in Rats: Implication for the Pathogenesis of Hypertensive Vascular Disease

“…Recent studies have suggested that non-receptor protein tyrosine kinases play an important role in transducing mechanical stimuli to biochemical pathways by coupling with integrin (Burridge et al 1992;Fukumoto et al 1996;Sieg et al 1998;Schlaepfer et al 1999;Ostergaard and Lysechko 2005;Ramjaun and Hodivala-Dilke 2009). Among them, focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that localizes to the point of cell contact with extracellular matrix and has been demonstrated to activate mitogen-activated protein kinases (MAPK) in response to integrin clustering in various types of cells (Burridge et al 1992;Sieg et al 1998;Schlaepfer et al 1999;Ostergaard and Lysechko 2005;Vadali et al 2007;Cai et al 2008).…”

“…Among them, focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that localizes to the point of cell contact with extracellular matrix and has been demonstrated to activate mitogen-activated protein kinases (MAPK) in response to integrin clustering in various types of cells (Burridge et al 1992;Sieg et al 1998;Schlaepfer et al 1999;Ostergaard and Lysechko 2005;Vadali et al 2007;Cai et al 2008). Proline-rich tyrosine kinase 2 (PYK2) is another non-receptor protein tyrosine kinase that has a high sequence homology to FAK, sharing 45% amino-acid sequence identity (Sieg et al 1998;Avraham et al 2000;Rocic et al 2002).…”