title: Regulation of the SRC family kinases by Csk.
abstract: The non-receptor tyrosine kinase Csk serves as an indispensable negative regulator of the Src family tyrosine kinases (SFKs) by specifically phosphorylating the negative regulatory site of SFKs, thereby suppressing their oncogenic potential. Csk is primarily regulated through its SH2 domain, which is required for membrane translocation of Csk via binding to scaffold proteins such as Cbp/PAG1. The binding of scaffolds to the SH2 domain can also upregulate Csk kinase activity. These regulatory features have been elucidated by analyses of Csk structure at the atomic levels. Although Csk itself may not be mutated in human cancers, perturbation of the regulatory system consisting of Csk, Cbp/PAG1, or other scaffolds, and certain tyrosine phosphatases may explain the upregulation of SFKs frequently observed in human cancers. This review focuses on the molecular bases for the function, structure, and regulation of Csk as a unique regulatory tyrosine kinase for SFKs.
authors.affiliation: Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Yamada-oka, Suita, Osaka, JAPAN. okadam@biken.osaka-u.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Okada
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D000081247:CSK Tyrosine-Protein Kinase; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D019061:src-Family Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
keywords: Csk; Src family; tyrosine kinases