Date of Award


Document Type


Degree Name

Master of Science (MS)



First Advisor

Bryan A. Ballif

Second Advisor

Jason Stumpff


CRK family adaptors are important mediators of cell adhesion, proliferation, and motility during both development and the oncogenic transformation of cells. CRK family adaptors bind to other proteins with their phosphotyrosine-binding SRC Homology 2 (SH2) domain and their proline-rich binding SRC Homology 3 (SH3) domains. CRK family SH2 domains selectively bind to a phosphorylated motif pYXXP (pY = phosphorylated tyrosine; X = any amino acid; P = proline). The SRC homology 2 domain-containing (SH) Protein family is the SH Protein family is enriched in YXXP sites, suggesting that its family members bind to CRK adaptor SH2 domains in a phosphorylation-dependent manner. The SH Protein family consists of four proteins: SHB, SHD, SHE, and SHF. Each SH Protein has an SH2 domain and six, five, four, and three YXXP sites, respectively. Mass spectrometry analysis of purified SH Proteins co-expressed in cells with the tyrosine kinase ABL, shows tyrosine phosphorylation of nearly all YXXP sites within the SH Protein family. This phosphorylation by ABL is both necessary and sufficient to induce direct binding of SH Proteins to the SH2 domains of CRK and CRKL.

As SH family proteins also have SH2 domains, we hypothesized they too would bind phosphotyrosine-containing substrates. We describe experiments characterizing SH Protein binding partners using immunopurified SH Proteins from stimulated cells, as well as using affinity chromatography using the SH2 domains of SH proteins as bait for proteins from cellular extracts. Together, our data imply that the binding of SH Proteins to CRK adaptors can relocate, amplify, and/or attenuate CRK adaptor function. The poorly-characterized SH Protein family and their binding domains and motifs are highly conserved across vertebrates. The present study provides important insights into their interaction networks and their molecular signaling mechanisms.



Number of Pages

128 p.

Available for download on Saturday, April 18, 2026

Included in

Biology Commons