General structure of SFKs. All SFKs share a common structure consisting of an N-terminal myristoyl group attached to an SH4 domain, a unique region, an SH3 domain, an SH2 domain, an SH2-kinase proline-rich linker region, and an SH1 or kinase domain. Yes, Fyn, Fgr, Lyn, Hck, and Lck contain a cysteine residue within the myristoylation peptide sequence that gets palmitoylated and mediates localization to lipid rafts. There is a conserved tyrosine residue in the activation loop and one in the C-terminal tail. Phosphorylation of the activation loop tyrosine by trans-autophosphorylation increases SFK activity, whereas phosphorylation of the C-terminal tyrosine by C-terminal Src kinase (Csk) or the structurally related Csk homologous kinase (Chk) inhibits SFK activity. Dephosphorylation of the activation loop and C-terminal inhibitory tyrosine residues by PTPs attenuates and increases SFK activity, respectively. Green denotes activation, and red denotes inhibition of SFK activity.