Ethanol‐Induced Cas Tyrosine Phosphorylation and Fyn Kinase Activation in Rat Brain

Abstract

Background: Tyrosine phosphorylation signaling has been reported to be involved in regulatory mechanisms of ethanol-induced modulation of the central nervous system. Methods:We investigated the effect of ethanol administration on tyrosine phosphorylation signaling in rat brain and also examined the possible involvement of Fyn kinase in the process.Results: Immunoprecipitation experiments showed that Crk-associated src substrate (Cas) was tyrosinephosphorylated in response to ethanol administration. Fyn kinase was shown to be activated by ethanol administration and to phosphorylate Cas on tyrosine residue in vitro. Furthermore, Fyn kinase was colocalized with Cas in rat cerebellum and cerebral cortex.Conclusions: Cas was tyrosine-phosphorylated in rat brain by ethanol administration, and Fyn kinase was most likely involved in the process.

RPTPα is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons

“…Nevertheless, in vitro studies showed that p130Cas is required for neurite extension in cerebellar neurons . Further, ethanol-stimulated Fyn-mediated p130Cas phosphorylation has been reported (Nishio and Suzuki, 2002). Once phosphorylated, p130Cas could signal to many different pathways that normally promote growth and not differentiation.…”

Crk-associated substrate (Cas) signaling protein functions with integrins to specify axon guidance during development

“…p130Cas and Cas-L transcripts are found in the developing and postnatal brain (Huang et al, 2006;Merrill et al, 2004), and p130Cas localizes to axons in early development and into adulthood in the spinal cord, cerebellum and cerebral cortex (Huang et al, 2006;Liu et al, 2007;Nishio and Suzuki, 2002). We used several antibodies that specifically recognize Cas proteins and examined their patterns of immunostaining in the developing rat spinal cord.…”

Targeting Cas Family Proteins as a Novel Treatment for Breast Cancer

“…Crk family: CrkI, CrkII, CrkL (Burnham et al 1996;Ishino et al 1995;Petruzzelli et al 1996;Sakai et al 1994a;Salgia et al 1996) Nck (Schlaepfer et al 1997) SHP-2 (Prasad et al 2001;Yo et al 2009) c-Src (Shin et al 2004) Serine-rich Domain 14-3-3 (Briknarova et al 2005) Carboxy-terminal domain AIP4 (Feng et al 2004) APC/C, CDH1 (Nourry et al 2004) Bmx/Etk (Abassi et al 2003) NSP family: BCAR3/NSP2, NSP1, CHAT (Gotoh et al 2000;Lu et al 1999;Sakakibara & Hattori 2000) Nephrocystin (Donaldson et al 2000) p130 Cas , HEF1, Id2 (Law et al 1999) p140Cap (Di Stefano et al 2004) PI3K (Li et al 2000) Src family: c-SRC, LCK, LYN, HCK, FYN, YES (Alexandropoulos & Baltimore 1996;Ishino et al 1995;Kanda et al 1999;Nakamoto et al 1996;Nasertorabi et al 2006;Nishio & Suzuki 2002;Pellicena & Miller 2001;Singh et al 2008) Not mapped/ indirect DDR (Shintani et al 2008) ER alpha (Cabodi et al 2004) Grb2 ) Smad3 (Liu et al 2000) …”

“…The SFKs are comprised of ten members of which c-Src, Lck, Lyn, Hck, Fyn, and Yes phosphorylate the SD of the Cas proteins (Alexandropoulos & Baltimore 1996;Ishino et al 1995;Kanda et al 1999;Nakamoto et al 1996;Nasertorabi et al 2006;Nishio & Suzuki 2002;Pellicena & Miller 2001;Singh et al 2008). In addition to phosphorylating the p130 Cas SD, cSrc binds to phosphorylated tyrosine residues within SD in vitro (Shin et al 2004).…”