The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains

Abstract

In recent years, members of the protein kinase family have been discovered at an accelerated pace. Most were first described, not through the traditional biochemical approach of protein purification and enzyme assay, but as putative protein kinase amino acid sequences deduced from the nucleotide sequences of molecularly cloned genes or complementary DNAs. Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members.

A cascade of Ca2+/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils

“…2A) [27]. A catalytically inactive, truncated form of CKLiK (CKLiK 296 -KD, for "kinase dead") was also generated, which contains an alanine substitution at Lys52, a putative ATP binding site that is essential for catalytic activity in conserved catalytic domains of CaMKI and CaMKIV [28][29][30]. Cytoplasmic localization of the full-length, constitutively active form of CKLiK was then demonstrated using a Western blot comparing nuclear versus cytoplasmic lysates from HEK293 cells transfected with either the FLAG-tagged, wild-type CKLiK or CKLiK 385 -CA (Fig.…”

Acidic substitution of the activation loop tyrosines in TrkA supports nerve growth factor-independent cell survival and neuronal differentiation

“…Since TrkA is most closely related to the IRK in the kinase superfamily (Hanks et al, 1988), we assayed the role of the activation loop tyrosines in the mechanism of TrkA activation. Speci®cally, we substituted Y 683 , Y 684 in rat TrkA with acidic amino acids in an e ort to disengage auto-inhibitory interactions with the catalytic base (Hubbard et al, 1994) and drive constitutive kinase activation.…”

“…Amino acid alignments between the b-chain of the insulin receptor kinase (IRK) and TrkA indicates that Tyr 679 , Tyr 683 and Tyr 684 in TrkA are the positional equivalents of the catalytic core residues, Tyr 1158 , Tyr 1162 and Tyr 1163 , in the IRK (Hanks et al, 1988). These observations suggest a model of TrkA activation based on crystallographic analyses of the IRK (Hubbard et al, 1994;Hubbard, 1997).…”

Disulfide relays and phosphorylative cascades: partners in redox-mediated signaling pathways

“…26 Phylogenetic analysis allows the protein kinase family to be divided into several subfamilies with finely tuned differences of sequence and structure, substrate selectivity and regulation properties. 27 In eukaryotes, a well-known distinction is between the serine/threonine protein kinases (STPK), such as mitogen-activated protein (MAP) kinases, protein kinase C (PKC), protein kinase B (Akt) and tumor growth factor-b (TGF-b) receptor, and the tyrosine kinases (PTK), such as receptor tyrosine kinases (EGF-R, VEGF-R, IGF-R), phosphatidylinositol-3 kinase and Janus kinase. This rough classification gives no information about the mode of action through which phosphorylation occurs.…”