My background is in mathematics, and not biology, so please bear with me. I am currently working on a project involving the effects of Epidermal growth factor treatment (EGF) on cell migration. I am reading a review of EGF signaling ([Epidermal growth factor receptor targeting in cancer: A review of trends and strategies](http://www.ncbi.nlm.nih.gov/pubmed/23953842) by Chetan Yewale, et. al.), and it states that "Various ligands can activate EGFR ... These ligands are expressed as integral membrane proteins." This statement makes absolutely no sense to me, and makes me question my understanding of signal transduction. I think of ligands as freely floating molecules that may eventually come into contact with the cell membrane and attach to some receptor. But a ligand expressed as an integral membrane protein? This seems contradictory to my understanding of ligands, which (I thought) are released from the cell in order to signal with cells (be it the same, neighbor, or distant cells). Integral membrane protein ligands would only be useful for autocrine signaling, which I don't think is true of EGF.
if i understand your question correctly- it may help to think of a membrane ligand as a lock on a door. you may also think of the lock as the receptor of the door. to open the door, the correct key is required. however the lock is always tied to the door so in that sense the lock is not free floating
