The proline rich tyrosine kinase 2 (PYK2) is a nonreceptor protein tyrosine kinase that is structurally related to FAK and thought to be important for leukocyte activation (Ostergaard & Lysechko, 2005). PYK2 tyrosine phosphorlation is known to occur downstream of IL-2 stimulation in human peripheral T lymphocytes. This phosphorylation can be prevented by blocking IL-2 mediated JAK activity. Although the function of Pyk2 within the IL-2 signaling pathways remains uncertain, a dominant negative mutant of Pyk2 inhibited IL-2-induced cell proliferation without affecting Stat5 activation which suggests that Pyk2 does indeed influence IL-2 driven immune cell responses.

The proline-rich tyrosine kinase 2 (PYK2) is a nonreceptor protein tyrosine kinase that is structurally related to FAK and thought to be important for leukocyte activation (Ostergaard & Lysechko 2005).
Coimmunoprecipitation experiments have demonstrated a physical association of Jak3 and Pyk2. A dominant interfering mutant of Pyk2 inhibited IL-2-induced cell proliferation without affecting Stat5 activation. Collectively, these results suggest that Pyk2 is a component of the Jak-mediated IL-2 signaling pathway, but a role has not been firmly established.

Protein-tyrosine kinase 2-beta (PTK2B, PYK2, FADK2), a cytosolic tyrosine kinase related to FAK, has been shown to complex with SIRP alpha.

Phosphorylation of S732 in FAK1 changes its conformation making Y407 accessible to Proline tyrosine kinase 2-beta (PTK2B). pY402-PTK2B then triggers the phosphorylation of FAK1 on Y407 (Le Boeuf et al. 2006). Phosphorylation of Y407 is required to recruit paxillin and vinculin to FAK1 and to ensure formation of focal adhesions and cell migration (Le Boeuf et al. 2004).

Proline tyrosine kinase 2-beta (PTK2B), also known as cell adhesion kinase-beta or related adhesion focal tyrosine kinase, is a nonreceptor protein-tyrosine kinase closely related to focal adhesion kinase (FAK1) that couples receptors, including integrins, with a variety of downstream effectors such as small G proteins belonging to the Ras and Rho families, mitogen-activated protein kinases, protein kinase C, and inositol phosphate metabolism (Avraham et al. 2000). PYK2B has been shown to play a critical role in the adhesion and migration of many cell types. PYK2B has been shown to localise to integrin and has been demonstrated to associate directly with integrin beta3 cytoplasmic tail (Butler & Blystone 2005, Duong & Rodan 2000, Le Boeuf et al. 2006).

Proline tyrosine kinase 2-beta (PTK2B/PYK2) is rapidly tyrosine phosphorylated on Y402 through Src-kinases in response to ligation of integrin beta3.

In its active GTP bound form, RHOU binds the following effectors:
ARHGAP30 (Naji et al. 2011; protein with GAP activity)
ARHGAP31 (Naji et al. 2011; protein with GAP activity)
GRB2 (Zhang et al. 2011; Bagci et al. 2020: weak binding)
ITSN2 (Gubar et al. 2020)
NCK2 (Saras et al. 2004; Bagci et al. 2020)
PAK1 (Tao et al. 2001; Shutes et al. 2004; Saras et al. 2004; Bagci et al. 2020)
PAK4 (Dart et al. 2015)
PAR6 (Brady et al. 2009)
PIK3R1 (Chuang et al. 2007; Bagci et al. 2020; protein with GAP activity)
PTK2B (Ruusala and Aspenström 2008)


The following candidate RHOU effectors were identified in the high throughput screen by Bagci et al. 2020:
ARHGEF6 (Bagci et al. 2020)
ARHGEF7 (Bagci et al. 2020)
CDC42 (Bagci et al. 2020)
CLTC (Bagci et al. 2020)
DEPDC1B (Bagci et al. 2020; protein with GAP activity)
DLG5 (Bagci et al. 2020)
DST (Bagci et al. 2020)
EPHA2 (Bagci et al. 2020)
GIT1 (Bagci et al. 2020)
GIT2 (Bagci et al. 2020)
HGS (Bagci et al. 2020)
IQGAP1 (Bagci et al. 2020)
MYO6 (Bagci et al. 2020)
NCK1 (Bagci et al. 2020)
PAK2 (Bagci et al. 2020)
PAK3 (Bagci et al. 2020)
PIK3R2 (Bagci et al. 2020; protein with GAP activity)
PEAK1 (Bagci et al. 2020)
SPTAN1 (Bagci et al. 2020)
SPTBN1 (Bagci et al. 2020)
SRGAP2 (Bagci et al. 2020; protein with GAP activity)
STAM (Bagci et al. 2020)
STAM2 (Bagci et al. 2020)
TXNL1 (Bagci et al. 2020)
USP9X (Bagci et al. 2020)
VANGL1 (Bagci et al. 2020)
WDR6 (Bagci et al. 2020)
WWP2 (Bagci et al. 2020)

RHOU does not bind WASL, a component of the WIP WASP complex (Bagci et al. 2020) and also does not bind:
CCP110 (Bagci et al. 2020)
CEP97 (Bagci et al. 2020)
MAP3K21 (Bagci et al. 2020)
MYH11 (Bagci et al. 2020)
MYL12B (Bagci et al. 2020)
SH3RF1 (Bagci et al. 2020)
TPM3 (Bagci et al. 2020)
TPM4 (Bagci et al. 2020)
ZNF512B (Bagci et al. 2020)