The chapter discusses the structural and functional analysis of the Crk protein, focusing on its phosphorylation state and interactions. One-dimensional 31P spectra of peptide I, peptide I plus a 50% excess of mCrk23, and p-mCrk are presented, showing a change in chemical shift that reflects a difference in pH. The monomeric nature of phosphorylated Crk is confirmed through centrifugation data. Hydrodynamic measurements and optical data are used to determine the molecular mass of the protein. The study also highlights the role of phosphorylation in regulating the SH2/SH3 adaptor function of Crk, suggesting that intramolecular SH2–pTyr interactions may inhibit intermolecular interactions involving the N-terminal SH3 domain. The findings support the idea that phosphorylation is a general mechanism for regulating the activities of SH2-containing proteins, including Src-family kinases. The research is supported by grants from the National Institutes of Health and the Canadian Institutes of Health Research.The chapter discusses the structural and functional analysis of the Crk protein, focusing on its phosphorylation state and interactions. One-dimensional 31P spectra of peptide I, peptide I plus a 50% excess of mCrk23, and p-mCrk are presented, showing a change in chemical shift that reflects a difference in pH. The monomeric nature of phosphorylated Crk is confirmed through centrifugation data. Hydrodynamic measurements and optical data are used to determine the molecular mass of the protein. The study also highlights the role of phosphorylation in regulating the SH2/SH3 adaptor function of Crk, suggesting that intramolecular SH2–pTyr interactions may inhibit intermolecular interactions involving the N-terminal SH3 domain. The findings support the idea that phosphorylation is a general mechanism for regulating the activities of SH2-containing proteins, including Src-family kinases. The research is supported by grants from the National Institutes of Health and the Canadian Institutes of Health Research.