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Deneka A , Korobeynikov V , Golemis EA
Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members
Gene. 2015 Oct 1;570(1) :25-35
PMID: 26119091    PMCID: PMC4519417    URL: https://www.ncbi.nlm.nih.gov/pubmed/26119091
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The CAS (Crk-associated substrate) adaptor protein family consists of four members: CASS1/BCAR1/p130Cas, CASS2/NEDD9/HEF1/Cas-L, CASS3/EFS/Sin and CASS4/HEPL. While CAS proteins lack enzymatic activity, they contain specific recognition and binding sites for assembly of larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes. All family members are intermediates in integrin-dependent signaling pathways mediated at focal adhesions, and associate with FAK and SRC family kinases to activate downstream effectors regulating the actin cytoskeleton. Most studies of CAS proteins to date have been focused on the first two members, BCAR1 and NEDD9, with altered expression of these proteins now appreciated as influencing disease development and prognosis for cancer and other serious pathological conditions. For these family members, additional mechanisms of action have been defined in receptor tyrosine kinase (RTK) signaling, estrogen receptor signaling or cell cycle progression, involving discrete partner proteins such as SHC, NSP proteins, or AURKA. By contrast, EFS and CASS4 have been less studied, although structure-function analyses indicate they conserve many elements with the better-known family members. Intriguingly, a number of recent studies have implicated these proteins in immune system function, and the pathogenesis of developmental disorders, autoimmune disorders including Crohn's disease, Alzheimer's disease, cancer and other diseases. In this review, we summarize the current understanding of EFS and CASS4 protein function in the context of the larger CAS family group.
Deneka, Alexander Korobeynikov, Vladislav Golemis, Erica A eng R21 CA181287/CA/NCI NIH HHS/ R01 GM089820/GM/NIGMS NIH HHS/ R01 GM083924/GM/NIGMS NIH HHS/ CA181287/CA/NCI NIH HHS/ GM089820/GM/NIGMS NIH HHS/ P30 CA006927/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review Netherlands Gene. 2015 Oct 1;570(1):25-35. doi: 10.1016/j.gene.2015.06.062. Epub 2015 Jun 26.